2-amino-thiazole derivatives, process for their preparation, and their use as antitumor agents

ABSTRACT

Compounds which are 2-amino-1,3-thiazole derivatives of formula (I)                  
 
wherein R is a halogen atom, a nitro group, an optionally substituted amino group or it is a group, optionally further substituted, selected from i) straight or branched C 1 –C 8  alkyl, C 2 –C 6  alkenyl or C 2 –C 6  alkynyl; ii) C 3 –C 6  cycloalkyl; iii) aryl or arylalkyl with from 1 to 8 carbon atoms within the straight or branched alkyl chain; R 1  is an optionally further substituted group selected from: i) straight or branched C 1 –C 8  alkyl or C 2 –C 6  alkenyl; ii) 3 to 6 membered carbocycle or 5 to 7 membered heterocycle ring; iii) aryl or arylcarbonyl; iv) arylalkyl with from 1 to 8 carbon atoms within the straight or branched alkyl chain; v) arylalkenyl with from 2 to 6 carbon atoms within the straight or branched alkenyl chain; vi) an optionally protected amino acid residue; or a pharmaceutically acceptable salt thereof; are useful for treating cell proliferative disorders associated with an altered cell dependent kinase activity.

The present invention relates to 2-amino-thiazole derivatives, to aprocess for their preparation, to pharmaceutical compositions containingthem and to their use as therapeutic agents, particularly in thetreatment of cancer and cell proliferative disorders.

Several cytotoxic drugs such as, e.g. fluorouracil (5-FU) doxorubicinand camptothecins result to damage DNA or to affect cellular metabolicpathways and thus cause, in many cases, an indirect block of the cellcycle. Therefore, by producing an irreversible damage to both normal andtumor cells, these agents result in a significant toxicity andside-effects. In this respect, compounds capable of being highlyspecific antitumor agents by selectively leading to tumor cell arrestand apoptosis, with comparable efficacy but reduced toxicity than thecurrently available drugs, are desirable.

It is well known in the art that progression through the cell cycle isgoverned by a series of checkpoint controls, otherwise referred to asrestriction points, which are regulated by a family of enzymes known asthe cyclindependent kinases (cdk). In their turn, the cdks themselvesare regulated at many levels such as, for instance, binding to cyclins.A normal progression through the cell cycle is controlled by thecoordinated activation and inactivation of different cyclin/cdkcomplexes. In G1, both cyclin D/cdk4 and cyclin E/cdk2 are thought tomediate the onset of S-phase. Progression through S-phase requires theactivity of cyclin A/cdk2 whereas the activation of cyclin A/cdc2 (cdk1)and cyclin B/cdc2 are required for the onset of metaphases.

For a general reference to cyclins and cyclin-dependent kinases see, forinstance, Kevin R. Webster et al. in Exp. Opin. Invest. Drugs, 1998,Vol. 7(6), 865–887.

Checkpoint controls are defective in tumor cells due, in part, todisregulation of cdk activity. For example, altered expression of cyclinE and cdk's has been observed in tumor cells, and deletion of the cdkinhibitor p27 KIP gene in mice has been shown to result in a higherincidence of cancer. Increasing evidence supports the idea that the cdksare rate-limiting enzymes in cell cycle progression and, as such,represent molecular targets for therapeutic intervention. In particular,the direct inhibition of cdk/cyclin kinase activity should be helpful inrestricting the unregulated proliferation of a tumor cell.

It has now been found that the 2-amino-1,3-thiazoles of the inventionare endowed with cdk/cyclin kinase inhibitory activity and are thususeful in therapy as antitumor agents whilst lacking, in terms of bothtoxicity and side effects, the aforementioned drawbacks known forcurrently available antitumor drugs. More specifically, the compounds ofthis invention are useful in the treatment of a variety of cancersincluding, but not limited to: carcinoma such as bladder, breast, colon,kidney, liver, lung, including small cell lung cancer, esophagus,gall-bladder, ovary, pancreas, stomach, cervix, thyroid, prostate, andskin, including squamous cell carcinoma; hematopoietic tumors oflymphoid lineage, including leukemia, acute lymphocitic leukemia, acutelymphoblastic leukemia, B-cell lymphoma, T-cell-lymphoma, Hodgkin'slymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma and Burkett'slymphoma; hematopoietic tumors of myeloid lineage, including acute andchronic myelogenous leukemias, myelodysplastic syndrome andpromyelocytic leukemia; tumors of mesenchymal origin, includingfibrosarcoma and rhabdomyosarcoma; tumors of the central and peripheralnervous system, including astrocytoma, neuroblastoma, glioma andschwannomas; other tumors, including melanoma, seminoma,teratocarcinoma, osteosarcoma, xenoderoma pigmentosum, keratoctanthoma,thyroid follicular cancer and Kaposi's sarcoma.

Due to the key role of cdks in the regulation of cellular proliferation,these 2-amino-1,3-thiazole derivatives are also useful in the treatmentof a variety of cell proliferative disorders such as, for instance,benign prostate hyperplasia, familial adenomatosis, polyposis,neuro-fibromatosis, psoriasis, vascular smooth cell proliferationassociated with atherosclerosis, pulmonary fibrosis, arthritis,glomerulonephritis and post-surgical stenosis and restenosis. Thecompounds of the invention can be useful in the treatment of Alzheimer'sdisease, as suggested by the fact that cdk5 is involved in thephosphorylation of tau protein (J. Biochem., 117, 741–749, 1995). Thecompounds of this invention, as modulators of apoptosis, could be usefulin the treatment of cancer, viral infections, prevention of AIDSdevelopment in HIV-infected individuals, autoimmune diseases andneurodegenerative disorder. The compounds of this invention could beuseful in inhibiting tumor angiogenesis and metastasis.

The compounds of this invention may also act as inhibitors of otherprotein kinases, e.g. protein kinase C, her2, raf1, MEK1, MAP kinase,EGF receptor, PDGF receptor, IGF receptor, PI3 kinase, wee1 kinase, Src,Abl and thus be effective in the treatment of diseases associated withother protein kinases.

Several 2-amino-1,3-thiazole derivatives are known in the art. Just fewexamples among them are 2-acetamido-, 2-propionamido- or2-butyramido-1,3-thiazole derivatives further substituted by halogenatoms in position 5 of the thiazole ring, which are reported asherbicides in JP 73027467 (Sankyo Co. Ltd.) or U.S. Pat. No. 3,374,082(The Upjohn Co.); 5-nitro-2-benzamido-1,3-thiazole is reported aspesticide in Ann. Rech. Vet., 22(4), 359–63, 1991;5-phenyl-2-acetamido-1,3-thiazoles further substituted onto phenyl ringare reported as synthetic intermediates (Chemical Abstracts, 1980,92:128793); and 5-dimethylaminomethyl- or5-diethylaminomethyl-2-acetamido-1,3-thiazole, both reported asherbicides in JP 71018564 (Japan Gas Chem Co.). Several other2-amino-1,3-thiazole derivatives have been reported in the art as usefultherapeutic agents. In particular, 5-methyl-1,3-thiazoles furthersubstituted in position 2 of the thiazole ring by abenzothiazinylcarbonylamino moiety, or derivatives thereof, have beendescribed as cyclooxygenase inhibitors; see, for instance, C.A.126(1997):301540. 2-Benzamido-1,3-thiazoles are disclosed in EP-A-261503(Valeas S.p.A.) as antiallergic agents;5-Alkyl-2-phenylalkylcarbonylamino-1,3-thiazoles further substitutedonto the phenyl ring with an alkenylcarbonyl or alkynylcarbonyl moietiesare disclosed in WO 98/04536 (Otsuka Pharmaceutical Co.) as proteinkinase C inhibitors. 5-Arylthio-2-acylamino-1,3-thiazole derivatives aredisclosed in EP-A-412404 (Fujisawa Pharm. Co.) as antitumor agents. Inaddition, among the compounds reported in the art as therapeutic agents,DE 2128941 (Melle-Bezons) discloses2-aminomethylcarbonylamino-5-chloro-1,3-thiazoles as antiinflammatory,sedative and analgesic agents; the compound2-diethylaminomethylcarbonylamino-5-chloro-1,3-thiazole beingspecifically exemplified therein.

Accordingly, the present invention provides the use of a compound whichis a 2-amino-1,3-thiazole derivative of formula (I)

wherein

-   -   R is a halogen atom, a nitro group, an optionally substituted        amino group or it is a group, optionally further substituted,        selected from:    -   i) straight or branched C₁–C₈ alkyl, C₂–C₆ alkenyl or C₂–C₆        alkynyl;    -   ii) C₃–C₆ cycloalkyl;    -   iii) aryl or arylalkyl with from 1 to 8 carbon atoms within the        straight or branched alkyl chain;    -   R₁ is an optionally further substituted group selected from:    -   i) straight or branched C₁–C₈ alkyl or C₂–C₆ alkenyl;    -   ii) 3 to 6 membered carbocycle or 5 to 7 membered heterocycle        ring;    -   iii) aryl or arylcarbonyl;    -   iv) arylalkyl with from 1 to 8 carbon atoms within the straight        or branched alkyl chain;    -   v) arylalkenyl with from 2 to 6 carbon atoms within the straight        or branched alkenyl chain;    -   vi) an optionally protected amino acid residue;        or a pharmaceutically acceptable salt thereof; in the        manufacture of a medicament for treating cell proliferative        disorders associated with an altered cell dependent kinase        activity.

According to a preferred embodiment of the invention, the said cellproliferative disorder is selected from the group consisting of cancer,Alzheimer's disease, viral infections, auto-immune diseases orneurodegenerative disorders. Preferably, the cancer is selected from thegroup consisting of carcinoma, squamous cell carcinoma, hematopoietictumors of myeloid or lymphoid lineage, tumors of mesenchymal origin,tumors of the central and peripheral nervous system, melanoma, seminoma,teratocarcinoma, osteosarcoma, xenoderoma pigmentosum, keratoctanthoma,thyroid follicular cancer and Kaposi's sarcoma.

According to another preferred embodiment of the invention, the cellproliferative disorder is selected from the group consisting of benignprostate hyperplasia, familial adenomatosis polyposis,neuro-fibromatosis, psoriasis, vascular smooth cell proliferationassociated with atherosclerosis, pulmonary fibrosis, arthritisglomerulonephritis and post-surgical stenosis and restenosis.

In addition, being useful in the treatment of cell proliferativedisorders associated with an altered cell dependent kinase activity,hence cell cycle inhibition or cdk/cyclin dependent inhibition, thecompounds of formula (I) of the invention also enable tumor angiogenesisand metastasis inhibition.

As above reported, some of the compounds of formula (I) of the inventionhave been reported in the art as useful therapeutic agents, for instanceas antiinflammatory, sedative and analgesic agents.

Therefore, it is a further object of the present invention a compoundwhich is a 2-amino-1,3-thiazole derivative of formula (I)

wherein

-   -   R is a halogen atom, a nitro group, an optionally substituted        amino group or it is a group, optionally further substituted,        selected from:    -   i) straight or branched C₁–C₈ alkyl, C₂–C₆ alkenyl or C₂–C₆        alkynyl;    -   ii) C₃–C₆ cycloalkyl;    -   iii) aryl or arylalkyl with from 1 to 8 carbon atoms within the        straight or branched alkyl chain;    -   R₁ is an optionally further substituted group selected from:    -   i) straight or branched C₁–C₈ alkyl or C₂–C₆ alkenyl;    -   ii) 3 to 6 membered carbocycle or 5 to 7 membered heterocycle        ring;    -   iii) aryl or arylcarbonyl;    -   iv) arylalkyl with from 1 to 8 carbon atoms within the straight        or branched alkyl chain;    -   v) arylalkenyl with from 2 to 6 carbon atoms within the straight        or branched alkenyl chain;    -   vi) an optionally protected amino acid residue;        or a pharmaceutically acceptable salt thereof; for use as a        medicament; provided that each of R and R₁, independently, is        not a methyl group and that the compound is not        2-diethylaminomethyl-carbonylamino-5-chloro-1,3-thiazole.

Among the compounds of formula (I) above reported, several derivativesresult to be novel.

Therefore, the present invention further provides a compound which is a2-amino-1,3-thiazole derivative of formula (I)

wherein

-   -   R is a halogen atom, a nitro group, an optionally substituted        amino group or it is a group, optionally further substituted,        selected from:    -   i) straight or branched C₁–C₈ alkyl, C₂–C₆ alkenyl or C₂–C₆        alkynyl;    -   ii) C₃–C₆ cycloalkyl;    -   iii) aryl or arylalkyl with from 1 to 8 carbon atoms within the        straight or branched alkyl chain;    -   R₁ is an optionally further substituted group selected from:    -   straight or branched C₁–C₈ alkyl or C₂–C₆ alkenyl;    -   ii) 3 to 6 membered carbocycle or 5 to 7 membered heterocycle        ring;    -   iii) aryl or arylcarbonyl;    -   iv) arylalkyl with from 1 to 8 carbon atoms within the straight        or branched alkyl chain;    -   v) arylalkenyl with from 2 to 6 carbon atoms within the straight        or branched alkenyl chain;    -   vi) an optionally protected amino acid residue;        or a pharmaceutically acceptable salt thereof; provided that:    -   a) R and R₁, each independently, are not methyl;    -   b) when R is bromine or chlorine then, R₁ is not unsubstituted        C₂–C₄ alkyl or an optionally substituted aminomethyl;    -   c) when R is nitro or phenyl, then R₁ is not unsubstituted        phenyl.

The compounds of formula (I) may have asymmetric carbon atoms and maytherefore exist either as racemic admixtures or as individual opticalisomers. Accordingly, all the possible isomers and their admixtures andof both the metabolites and the pharmaceutically acceptablebio-precursors (otherwise referred to as pro-drugs) of the compounds offormula (I), as well as the uses thereof, are also within the scope ofthe present invention.

In the present description, unless otherwise specified, with the termhalogen atom we intend a chlorine, bromine, fluorine or iodine atom.

With the term optionally substituted amino group we intend an aminogroup wherein one or both hydrogen atoms are optionally replaced byother substituents which are the same or different, as set forth below.

With the term straight or branched C₁–C₈ alkyl we intend a group suchas, for instance, methyl, ethyl, n.propyl, isopropyl, n.butyl, isobutyl,sec-butyl, tert-butyl, n.pentyl, n.hexyl, n.heptyl, n.octyl and thelike.

With the term straight or branched C₂–C₆ alkenyl or alkynyl we intend agroup such as, for instance, vinyl, allyl, isopropenyl, 1-, 2- or3-butenyl, isobutylenyl, pentenyl, hexenyl, ethynyl, 1- or 2-propynyl,butynyl, pentynyl, hexynyl and the like.

With the term C₃–C₆ cycloalkyl we intend a cyclopropyl, cyclobutyl,cyclopentyl or cyclohexyl group.

With the term aryl, either as such or as arylalkyl, arylalkenyl,arylcarbonyl and the like, we intend a mono-, bi- or poly- eithercarbocyclic as well as heterocyclyc hydrocarbon with from 1 to 4 ringmoieties, either fused or linked to each other by single bonds, whereinat least one of the carbocyclic or heterocyclic rings is aromatic.Examples of aryl groups are phenyl, indanyl, biphenyl, α- or β-naphthyl,fluorenyl, 9,10-dihydroanthracenyl, pyridyl, pyrazinyl, pyrimidinyl,pyridazinyl, indolyl, imidazolyl, 1,2-methylenedioxyphenyl, thiazolyl,isothiazolyl, pyrrolyl, pyrrolyl-phenyl, furyl, phenyl-furyl,benzotetrahydrofuran, oxazolyl, isoxazolyl, pyrazolyl, chromenyl,thienyl, benzothienyl, isoindolinyl, benzoimidazolyl, tetrazolyl,tetrazolylphenyl, pyrrolidinyl-tetrazolyl, isoindolinyl-phenyl,quinolinyl, isoquinolinyl, 2,6-diphenyl-pyridyl, quinoxalinyl,pyrazinyl, phenyl-quinolyl, benzofurazanyl, 1,2,3-triazole,1-phenyl-1,2,3-triazole, and the like.

With the term 3 to 6 membered carbocycle, hence encompassing but notlimited to C₃–C₆ cycloalkyl groups, we also intend an unsaturatedcarbocyclic hydrocarbon such as, for instance, cyclopentylene orcyclohexylene.

With the term 5 to 7 membered heterocycle, hence encompassing aromaticheterocycles also referred to as aryl groups, we further intend asaturated or partially unsaturated 5 to 7 membered carbocyle wherein oneor more carbon atoms are replaced by heteroatoms such as nitrogen,oxygen and sulphur. Examples of 5 to 7 membered heterocycles, optionallybenzocondensed or further substituted, are 1,3-dioxolane, pyran,pyrrolidine, pyrroline, imidazolidine, pyrazolidine, pyrazoline,piperidine, piperazine, N-alkyl-piperazine, morpholine, tetrahydrofuranand the like.

With the term amino acid residue we intend the residue of a naturalα-amino acid of formula HOOC—R₁, wherein R₁ is bonded to thethiazole-NH—C(═O)— moiety and is represented by a —CH(Z)NHY groupwherein Z is the characterising portion of the amino acid and Y ishydrogen or a suitable amino protecting group such as, for instance,tertbutoxycarbonyl or benzyloxycarbonyl. Examples of α-amino acids arealanine, isoleucine, glycine, lysine, arginine, cystine, histidine,leucine, proline and the like.

According to the above indicated substituent meanings, any of the aboveR and R₁ groups may be optionally substituted in any of the freepositions by one or more groups, for instance 1 to 6 groups, selectedfrom: halogen, nitro, oxo groups (═O), carboxy, cyano, alkyl,perfluorinated alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycyl;amino groups and derivatives thereof such as, for instance, alkylamino,alkoxycarbonylalkylamino, dialkylamino, arylamino, diarylamino orarylureido; carbonylamino groups and derivatives thereof such as, forinstance, hydrogenocarbonylamino (HCONH—), alkylcarbonylamino,alkenylcarbonylamino, arylcarbonylamino, alkoxycarbonylamino;oxygen-substituted oximes such as, for instance,alkoxycarbonylalkoxyimino or alkoxyimino; hydroxy groups and derivativesthereof such as, for instance, alkoxy, aryloxy, alkylcarbonyloxy,arylcarbonyloxy, cycloalkenyloxy; carbonyl groups and derivativesthereof such as, for instance, alkylcarbonyl, arylcarbonyl,alkoxycarbonyl, aryloxycarbonyl, cycloalkyloxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl; sulfurated derivatives suchas, for instance, alkylthio, arylthio, alkylsulphonyl, arylsulphonyl,alkylsulphinyl, arylsulphinyl, arylsulphonyloxy, aminosulfonyl,alkylaminosulphonyl or dialkylaminosulphonyl. In their turn, wheneverappropriate, each of the above possible substituents on R and R₁ may befurther substituted by one or more of the aforementioned groups.Examples of compounds of formula (I) wherein R and R₁ groups aresubstituted by one or more of the aforementioned substituents which, intheir turn, are optionally further substituted as set forth above, aregiven below.

Pharmaceutically acceptable salts of the compounds of formula (I) arethe acid addition salts with inorganic or organic, e.g. nitric,hydrochloric, hydrobromic, sulphuric, perchloric, phosphoric, acetic,trifluoroacetic, propionic, glycolic, lactic, oxalic, malonic, malic,maleic, tartaric, citric, benzoic, cinnamic, mandelic, methanesulphonic,isethionic and salicylic acid, as well as the salts with inorganic ororganic bases, e.g. alkali or alkaline-earth metals, especially sodium,potassium, calcium or magnesium hydroxides, carbonates or bicarbonates,acyclic or cyclic amines, preferably methylamine, ethylamine,diethylamine, triethylamine or piperidine.

The compounds of formula (I) may have asymmetric carbon atoms and maytherefore exist either as racemic admixtures or as individual opticalisomers. Accordingly, the use as an antitumor agent of all the possibleisomers and their admixtures and of both the metabolites and thepharmaceutically acceptable bioprecursors (otherwise referred to aspro-drugs) of the compounds of formula (I) are also within the scope ofthe present invention.

Preferred compounds of formula (I), according to the present invention,are 2-amino-1,3-thiazole derivatives wherein R is a halogen atom or anoptionally substituted group selected from a straight or branched C₁–C₄alkyl, C₃–C₆ cycloalkyl, aryl or an arylalkyl with from 1 to 4 carbonatoms within the alkyl chain; R₁ is an optionally substituted groupselected from straight or branched C₁–C₄ alkyl or alkenyl, aryl orarylalkyl with from 1 to 4 carbon atoms within the alkyl chain or it isan optionally protected amino acid residue.

Still more preferred compounds, within this class, are the derivativesof formula (I) wherein R is a bromine or chlorine atom or is anoptionally substituted group selected from straight or branched C₁–C₄alkyl, cyclopropyl, aryl or arylalkyl with from 1 to 2 carbon atomswithin the alkyl chain; R₁ is an optionally substituted group selectedfrom straight or branched C₁–C₄ alkyl or alkenyl, aryl or arylalkyl withfrom 1 to 4 carbon atoms within the alkyl chain or it is an optionallyprotected amino acid residue.

Another class of preferred compounds of the invention are the compoundsof formula (I)

wherein

-   -   R is a halogen atom or is selected from nitro, amino,        alkylamino, hydroxyalkylamino, arylamino, C₃–C₆ cycloalkyl and        straight or branched C₁–C₆ alkyl which is unsubstituted or        substituted by hydroxy, alkylthio, alkoxy, amino, alkylamino,        alkoxycarbonylamino, alkoxycarbonylalkylamino, alkylcarbonyl,        alkylsulfonyl, alkoxycarbonyl, carboxy or aryl which is        unsubstituted or substituted by one or more hydroxy, halogen,        nitro, alkoxy, aryloxy, alkylthio, arylthio, amino, alkylamino,        dialkylamino, N-alkyl-piperazinyl, 4-morpholinyl, arylamino,        cyano, alkyl, phenyl, aminosulfonyl, aminocarbonyl,        alkylcarbonyl, arylcarbonyl, alkoxycarbonyl or carboxy groups,        or R is an aryl group which is unsubstituted or substituted by        one or more hydroxy, halogen, nitro, alkoxy, aryloxy, alkylthio,        arylthio, amino, alkylamino, dialkylamino, N-alkyl-piperazinyl,        4-morpholinyl, arylamino, cyano, alkyl, phenyl, aminosulphonyl,        aminocarbonyl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl or        carboxy groups;    -   R₁ is a straight or branched C₁–C₆ alkyl group or an aryl group,        each being unsubstituted or substituted as defined above for R;        or a pharmaceutically acceptable salt thereof; provided that:    -   a) R and R₁, each independently, are not methyl;    -   b) when R is bromine or chlorine then, R₁ is not unsubstituted        C₂–C₄ alkyl or an optionally substituted aminomethyl;    -   c) when R is nitro or phenyl, then R₁ is not unsubstituted        phenyl.

Examples of preferred compounds of the invention, whenever appropriatein the form of pharmaceutically acceptable salts, e.g. hydrobromide orhydrochloride salt, are the following:

-   1. ethyl 3-[(5-bromo-1,3-thiazol-2-yl)amino]-3-oxopropanoate;-   2. N-(5-bromo-1,3-thiazol-2-yl)-2-phenyl-acetamide;-   3. N-(5-bromo-1,3-thiazol-2-yl)-benzamide;-   4. Ethyl 4-[(5-bromo-1,3-thiazol-2-yl)amino]-4-oxobutanoate;-   5. N-(5-Bromo-thiazol-2-yl)-3-hydroxy-propionamide;-   6. N-(5-Bromo-1,3-thiazol-2-yl)-4-hydroxybutanamide;-   7. N-(5-Bromo-thiazol-2-yl)-2-ethoxy-acetamide;-   8. 2-N-[2-(3-pyridyl)-acetyl-amino]-5-bromo-thiazole;-   9. 2-N-[2-(3-pyridyl)-acetyl-amino]-5-isopropyl-thiazole;-   10. N-(5-bromo-1,3-thiazol-2-yl)-2-(3-hydroxyphenyl)acetamide;-   11. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-hydroxyphenyl)acetamide-   12. N-(5-bromo-1,3-thiazol-2-yl)-2-(3-methoxyphenyl)acetamide;-   13. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-methoxyphenyl)acetamide;-   14. N-(5-bromo-1,3-thiazol-2-yl)-2-(3-chorophenyl)acetamide;-   15. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-chorophenyl)acetamide;-   16. N-(5-bromo-1,3-thiazol-2-yl)-2-(4-hydroxyphenyl)acetamide;-   17. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-hydroxyphenyl)acetamide;-   18. N-(5-bromo-1,3-thiazol-2-yl)-2-(3,4-dihydroxyphenyl)acetamide;-   19.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4-dihydroxyphenyl)acetamide;-   20.    N-(5-bromo-1,3-thiazol-2-yl)-2-(4-hydroxy-3-methoxyphenyl)acetamide;-   21.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-hydroxy-3-methoxyphenyl)acetamide;-   22. N-(5-bromo-1,3-thiazol-2-yl)-2-(4-methoxyphenyl)acetamide;-   23. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methoxyphenyl)acetamide;-   24. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-chlorophenyl)acetamide;-   25. N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-acetamide;-   26. N-(5-bromo-thiazol-2-yl)-4-sulfamoyl-benzamide;-   27. N-(5-isopropyl-thiazol-2-yl)-4-sulfamoyl-benzamide;-   28. 4-amino-N-(5-bromo-1,3-thiazol-2-yl)butanamide;-   29. 3-amino-N-(5-bromo-1,3-thiazol-2-yl) propionamide;-   30. N-(5-isopropyl-1,3-thiazol-2-yl)-butanamide;-   31. N-(5-bromo-1,3-thiazol-2-yl)-butanamide;-   32. N-(5-chloro-1,3-thiazol-2-yl)-butanamide;-   33. N-(5-phenyl-1,3-thiazol-2-yl)-butanamide;-   34. N-(5-nitro-1,3-thiazol-2-yl)-butanamide;-   35. N-(5-methyl-1,3-thiazol-2-yl)-butanamide;-   36. N-(5-benzyl-1,3-thiazol-2-yl)-butanamide;-   37. N-(5-isobutyl-1,3-thiazol-2-yl)-butanamide;-   38. N-(5-cyclopropyl-1,3-thiazol-2-yl)-butanamide;-   39. N-{5-[2-(methylsulfonyl)ethyl]-1,3-thiazol-2-yl}-butanamide;-   40. N-[5-(2-methylthioethyl)-1,3-thiazol-2-yl]-butanamide;-   41. N-{5-[2-(methoxycarbonyl)ethyl]-1,3-thiazol-2-yl}butanamide;-   42. N-[5-(3-methoxy-propyl)-1,3-thiazol-2-yl]-butanamide;-   43. N-[5-(2-ethoxy-ethyl)-1,3-thiazol-2-yl]-butanamide;-   44. N-[5-(indol-3-yl-methyl)-1,3-thiazol-2-yl]-butanamide;-   45. N-[5-(3-oxo-butyl)-1,3-thiazol-2 yl]-butanamide;-   46.    2-[3-(3-chloropropoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   47. 2-[3-(2-chloroethoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)    acetamide-   48. 2-(4-aminophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   49. 4-amino-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   50.    2-(2-amino-1,3-thiazol-4-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   51.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-{3-[3-(4-morpholinyl)propoxy]phenyl}acetamide-   52.    N-(5-isopropyl-1,3-thiazol-2′-yl)-2-{3-[2-(4-morpholinyl)ethoxy]phenyl}acetamide-   53.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-{3-[3-(1-pirrolidinyl)propoxy]phenyl}acetamide-   54.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-{3-[3-(4-methyl-1-piperazinyl)propoxy]phenyl}acetamide-   55.    2-{3-[2-(dimethylamino)ethoxy]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;-   56.    2-{3-[3-(dimethylamino)propoxy]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   57.    2-[4-(dimethylamino)phenyl]-N-(5-isobutyl-1,3-thiazol-2-yl)acetamide-   58.    2-(1,3-benzodioxol-5-yl)-N-(5-isobutyl-1,3-thiazol-2-yl)acetamide-   59.    N-(5-benzyl-1,3-thiazol-2-yl)-2-[4-(dimethylamino)phenyl]acetamide-   60.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[3-(2-methoxyethoxy)-phenyl]acetamide-   61.    3-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-(4-methyl-1-piperazinyl)benzamide-   62. N-(5-isobutyl-1,3-thiazol-2-yl)-2-(3-pyridinyl)acetamide-   63. N-(5-benzyl-1,3-thiazol-2-yl)-2-(3-pyridinyl)acetamide-   64.    2′-[N-[2′-N′-(ethoxycarbonyl-methyl)-amino]-acetyl]amino-5-bromo-thiazole-   65. 2-anilino-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   66. (R)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylpropanamide-   67. (S)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylpropanamide-   68. N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   69. 2,5-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   70. 3,5-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   71. 3,4-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   72. 2,4-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   73. 2,3-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   74. 3-iodio-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   75. 2-iodio-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   76. 4-iodio-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   77. 3-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   78. 4-chloro-2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   79. 5-bromo-2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   80. 3-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   81. 2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   82. 4-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   83. 3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   84. 2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   85. 4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   86. 2,4-difluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   87. 3,4-difluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   88. 2,3,4,5,6-pentafluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   89. N-(5-isopropyl-1,3-thiazol-2-yl)-4-methyl-3-nitrobenzamide-   90. N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-nitrobenzamide-   91. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methyl-2-nitrobenzamide-   92. N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethyl-4-nitrobenzamide-   93. N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxy-2-nitrobenzamide-   94. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-2-nitrobenzamide-   95. N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxy-3-nitrobenzamide-   96. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-4-nitrobenzamide-   97. N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dinitrobenzamide-   98. 5-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-nitrophenyl    octanoate-   99. N-(5-isopropyl-1,3-thiazol-2-yl)-3-nitrobenzamide-   100. N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide-   101. N-(5-isopropyl-1,3-thiazol-2-yl)-4-nitrobenzamide-   102.    N-(5-isopropyl-1,3-thiazol-2-yl)-4-(methylsulfonyl)-3-nitrobenzamide-   103. 4-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-nitrobenzamide-   104. 6-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-nitrobenzamide-   105. 4-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide-   106. 2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-nitrobenzamide-   107. 5-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide-   108. 2-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)-5-nitrobenzamide-   109. 4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-nitrobenzamide-   110. 4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide-   111.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitro-4-(trifluoromethyl)benzamide-   112.    N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-bis(trifluoromethyl)benzamide-   113.    N-(5-isopropyl-1,3-thiazol-2-yl)-2,6-bis(trifluoromethyl)benzamide-   114. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(trifluoromethyl)benzamide-   115. N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide-   116.    3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-(trifluoromethyl)benzamide-   117.    2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide-   118.    5-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide-   119.    2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-(trifluoromethyl)benzamide-   120.    4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide-   121. methyl    4-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}benzoate-   122. methyl    2-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}benzoate-   123. 4-cyano-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   124. 3-cyano-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   125. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methylbenzamide-   126. N-(5-isopropyl-1,3-thiazol-2-yl)-2-methylbenzamide-   127. N-(5-isopropyl-1,3-thiazol-2-yl)-2-methylbenzamide-   128. N-(5-isopropyl-1,3-thiazol-2-yl)-4-vinylbenzamide-   129. N-(5-isopropyl-1,3-thiazol-2-yl)-4-(2-phenylethynyl)benzamide-   130. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-4-methylbenzamide-   131. 2-benzyl-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   132. N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenethylbenzamide-   133. N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylbenzamide-   134. N-(5-isopropyl-1,3-thiazol-2-yl)-4-phenylbenzamide-   135. 4-(tert-butyl)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   136. N-(5-isopropyl-1,3-thiazol-2-yl)-4-isopropylbenzamide-   137. N-(5-isopropyl-1,3-thiazol-2-yl)-4-pentylbenzamide-   138. 3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methylbenzamide-   139. N-(5-isopropyl-1,3-thiazol-2-yl)-3,4-dimethylbenzamide-   140. N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethylbenzamide-   141. 4-acetyl-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   142. N-(5-isopropyl-1,3-thiazol-2-yl)-4-(methylsulfonyl)benzamide-   143.    5-(aminosulfonyl)-2,4-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   144.    5-(aminosulfonyl)-4-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   145. 3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxybenzamide-   146. 3-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxybenzamide-   147. 5-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxybenzamide-   148. N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxybenzamide-   149. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxybenzamide-   150. N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxybenzamide-   151. N-(5-isopropyl-1,3-thiazol-2-yl)-3,4-dimethoxybenzamide-   152. N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethoxybenzamide-   153. N-(5-isopropyl-1,3-thiazol-2-yl)-2,4-dimethoxybenzamide-   154. N-(5-isopropyl-1,3-thiazol-2-yl)-2,3-dimethoxybenzamide-   155. N-(5-isopropyl-1,3-thiazol-2-yl)-3-phenoxybenzamide-   156. N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenoxybenzamide-   157. N-(5-isopropyl-1,3-thiazol-2-yl)-4-phenoxybenzamide-   158. 2-ethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   159. 4-ethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   160. N-(5-isopropyl-1,3-thiazol-2-yl)-3,4,5-trimethoxybenzamide-   161. 3,4-diethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   162. 3,4,5-triethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   163.    N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-4-(methoxymethoxy)benzamide-   164. 4-butoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   165. N-(5-isopropyl-1,3-thiazol-2′-yl)-4-propoxybenzamide-   166. 4-isopropoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   167. N-(5-isopropyl-1,3-thiazol-2-yl)-1,3-benzodioxole-5-carboxamide-   168. 4-(benzyloxy)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   169.    4-(2-cyclohexen-1-yloxy)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   170. N-(5-isopropyl-1,3-thiazol-2-yl)-4-(trifluoromethoxy)benzamide-   171. 4-(difluoromethoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   172. N-(5-isopropyl-1,3-thiazol-2-yl)-4-(methylsulfanyl)benzamide-   173.    2-[(4-chlorophenyl)sulfinyl]-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   174.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[(4-nitrophenyl)sulfinyl]benzamide-   175.    N-(5-isopropyl-1,3-thiazol-2-yl)-4-[(4-methylphenyl)sulfonyl]-3-nitrobenzamide-   176.    N-(5-isopropyl-1,3-thiazol-2-yl)-3-[trifluoromethyl)sulfanyl]benzamide-   177.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxy-4-(methylsulfanyl)benzamide-   178.    2-[(2-cyanophenyl)sulfanyl]-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   179.    N˜1,N˜1˜-diethyl-3,6-difluoro-N˜2˜-(5-isopropyl-1,3-thiazol-2-yl)phthalamide-   180. 4-formyl-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   181. 2-formyl-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   182.    4-{[(2,5-dimethoxyanilino)carbonyl]amino}-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   183. 4-(hydroxymethyl)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   184. 4-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-nitrobenzyl    acetate-   185. 4-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-nitrobenzyl    4-(acetylamino)-3-iodobenzoate-   186. 4-(acetylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   187.    N-(5-isopropyl-1,3-thiazol-2-yl)-4-[(2-phenylacetyl)amino]benzamide-   188.    4-(acetylamino)-3-iodo-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   189. 4-amino-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   190. 4-(dimethylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   191. 3-(dimethylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   192. 2-(methylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   193.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[3-(trifluoromethyl)anilino]benzamide-   194.    3-{[5-bromo-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]amino}-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   195. N-(5-isopropyl-1,3-thiazol-2-yl)-4-(1H-pyrrol-1-yl)benzamide-   196. 2,6-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)isonicotinamide-   197.    2-(4-bromophenyl)-6-(4-iodophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)isonicotinamide-   198.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[3-(trifluoromethyl)anilino]nicotinamide-   199. 2,6-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)nicotinamide-   200. 5,6-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)nicotinamide-   201. 2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-6-methylnicotinamide-   202.    2,6-dichloro-5-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)nicotinamide-   203. N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenoxynicotinamide-   204.    N-(5-isopropyl-1,3-thiazol-2-yl)-6-(2,2,2-trifluoroethoxy)nicotinamide-   205. N-(5-isopropyl-1,3-thiazol-2-yl)-2,6-dimethoxynicotinamide-   206. N-(5-isopropyl-1,3-thiazol-2-yl)-2-quinoxalinecarboxamide-   207. N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-pyrazinecarboxamide-   208. N-(5-isopropyl-1,3-thiazol-2-yl)-8-quinolinecarboxamide-   209.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-4-quinolinecarboxamide-   210.    N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide-   211.    N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-1H-pyrazole-3-carboxamide-   212. N-(5-isopropyl-1,3-thiazol-2-yl)-1H-pyrazole-4-carboxamide-   213.    N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-phenyl-2H-1,2,3-triazole-4-carboxamide-   214.    2-[(2,1,3-benzoxadiazol-5-yloxy)methyl]-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methyl-1,3-thiazole-5-carboxamide-   215. N-(5-isopropyl-1,3-thiazol-2-yl)-9H-fluorene-1-carboxamide-   216.    N-(5-isopropyl-1,3-thiazol-2-yl)-7-methoxy-1-benzofuran-2-carboxamide-   217.    N-(5-isopropyl-1,3-thiazol-2-yl)-1-[(4-methylphenyl)sulfonyl]-1H-pyrrole-3-carboxamide-   218. 2-ethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)-1-naphthamide-   219. 4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-1-naphthamide-   220. N-(5-isopropyl-1,3-thiazol-2-yl)-2-naphthamide-   221.    N-(5-isopropyl-1,3-thiazol-2-yl)-9,10-dioxo-9,10-dihydro-2-anthracenecarboxamide-   222.    N-(5-isopropyl-1,3-thiazol-2-yl)-9-oxo-9H-fluorene-4-carboxamide-   223.    N-(5-isopropyl-1,3-thiazol-2-yl)-9-oxo-9H-fluorene-1-carboxamide-   224.    N-(5-isopropyl-1,3-thiazol-2-yl)-8-oxo-5,6,7,8-tetrahydro-2-naphthalenecarboxamide-   225.    N-(5-isopropyl-1,3-thiazol-2-yl)-1,3-dioxo-1,3-dihydro-2-benzofuran-5-carboxamide-   226. N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-5-carboxamide-   227. N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-4-carboxamide-   228.    N-(5-isopropyl-1,3-thiazol-2-yl)-1-methyl-2-phenyl-1H-indole-5-carboxamide-   229.    2-butyl-N-(5-isopropyl-1,3-thiazol-2-yl)-1-methyl-1H-indole-5-carboxamide-   230. N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-6-carboxamide-   231.    N-(5-isopropyl-1,3-thiazol-2-yl)-5-methoxy-1H-indole-2-carboxamide-   232.    1-allyl-2-butyl-N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-5-carboxamide-   233.    N-(5-isopropyl-1,3-thiazol-2-yl)-1-methyl-1H-indole-2-carboxamide-   234.    1-benzyl-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-1H-indole-5-carboxamide-   235.    N-(5-isopropyl-1,3-thiazol-2-yl)-1H-1,2,3-benzotriazole-5-carboxamide-   236.    N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethyl-4-isoxazolecarboxamide-   237. N-(5-isopropyl-1,3-thiazol-2-yl)-3-thiophenecarboxamide-   238.    N-(5-isopropyl-1,3-thiazol-2-yl)-3-methyl-2-thiophenecarboxamide-   239.    N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-thiophenecarboxamide-   240. 5-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)-2-thiophenecarboxamide-   241.    N-(5-isopropyl-1,3-thiazol-2-yl)-3-[(2,3,3-trichloroacryloyl)amino]-2-thiophenecarboxamide-   242. 5-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide-   243. N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide-   244. N-(5-isopropyl-1,3-thiazol-2-yl)-5-(4-nitrophenyl)-2-furamide-   245. N-(5-isopropyl-1,3-thiazol-2-yl)-5-(2-nitrophenyl)-2-furamide-   246. 5-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide-   247.    N-(5-isopropyl-1,3-thiazol-2-yl)-5-[3-(trifluoromethyl)phenyl]-2-furamide-   248.    5-(4-chloro-2-nitrophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide-   249.    N-(5-isopropyl-1,3-thiazol-2-yl)-5-(4-methyl-2-nitrophenyl)-2-furamide-   250.    5-[2-chloro-5-(trifluoromethyl)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide-   251. tert-butyl    (1R)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-phenylethylcarbamate-   252.    (1R)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-phenylethyl    acetate-   253.    (1S)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-phenylethyl    acetate-   254.    (R,S)-2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide-   255. (R)-2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide-   256. (S)-2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide-   257.    2-(acetylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide-   258.    (R,S)-2-(methoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide-   259.    (R)-2-(methoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide-   260.    (S)-2-(methoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide-   261.    3,3,3-trifluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxy-2-phenylpropanamide-   262. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(1-naphthyl)acetamide-   263. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-naphthyl)acetamide-   264. 2-(1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   265.    2-(1,3-benzodioxol-4-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   266. 2-(2,4-dinitrophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   267.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-methyl-1H-indol-3-yl)acetamide-   268.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(1-methyl-1H-indol-3-yl)acetamide-   269.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(5-methoxy-1H-indol-3-yl)acetamide-   270.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(5-benzyloxy-1H-indol-3-yl)acetamide-   271.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-methoxy-2-methyl-1H-indol-3-yl)acetamide-   272.    2-(1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-oxoacetamide-   273.    2-(5-bromo-1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   274.    2-(5-fluoro-1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   275.    2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   276. 3-(1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide-   277. 4-(1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)butanamide-   278. N-(5-isopropyl-1,3-thiazol-2-yl)-3-(2-thienyl)propanamide-   279. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-thienyl)acetamide-   280. N-(5-isopropyl-1,3-thiazol-2-yl)-2-oxo-2-(2-thienyl)acetamide-   281. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-thienyl)acetamide-   282.    2-(5-chloro-1-benzothiophen-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   283.    2-(1-benzothiophen-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   284.    2-[2-(formylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)-2-(methoxyimino)acetamide-   285.    2-{2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)-2-(methoxyimino)acetamide-   286.    2-chloro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide-   287. ethyl    2-({[2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-(1H-pyrazol-3-yl)ethylidene]amino}oxy)acetate-   288. 2-(2-furyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-oxoacetamide-   289.    2-(5-bromo-3-pyridinyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   290.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(7-methoxy-2-oxo-2H-chromen-4-yl)acetamide-   291. N-(5-isopropyl-1,3-thiazol-2-yl)-4-phenyl-3-butenamide-   292.    N-(5-isopropyl-1,3-thiazol-2-yl)-4-oxo-4-(4-methylphenyl)butanamide-   293. N-(5-isopropyl-1,3-thiazol-2-yl)-4-(4-nitrophenyl)butanamide-   294. N-(5-isopropyl-1,3-thiazol-2-yl)-4-phenylbutanamide-   295. benzyl    4-[(5-isopropyl-1,3-thiazol-2-yl)amino-4-oxobutylcarbamate-   296. methyl 5-[(5-isopropyl-1,3-thiazol-2-yl)amino]-5-oxopentanoate-   297.    4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)butanamide-   298.    N-(5-isopropyl-1,3-thiazol-2-yl)-4-(4-methoxy-1-naphthyl)-4-oxobutanamide-   299. 3-(2-chlorophenoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide-   300. 3-(4-methylphenoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide-   301. 3-cyclopentyl-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide-   302. 3-cyclohexyl-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide-   303. N-(5-isopropyl-1,3-thiazol-2-yl)-4-methylpentanamide-   304. 3-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide-   305. 3-(4-methoxyphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide-   306. 3-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide-   307. 3-phenyl-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide-   308. 2-cyclohexyl-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   309. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methylbutanamide-   310. N-(5-isopropyl-1,3-thiazol-2-yl)-5-oxo-5-phenylpentanamide-   311. 2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-phenylethyl    acetate-   312.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-(1-oxo-1,3-dihydro-9H-isoindol-2-yl)phenyl]propanamide-   313.    1-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)cyclopentanecarboxamide-   314.    1-phenyl-N-(5-isopropyl-1,3-thiazol-2-yl)cyclopentanecarboxamide-   315.    2-(3-bromo-4-methoxyphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   316.    2-(2-nitro-4-trifluoromethylphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   317. 5-cyclohexyl    1-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}benzyl)(2S)-2-[(tert-butoxycarbonyl)amino]pentanedioate-   318.    2-(5,6-dimethyl-1H-benzimidazol-1-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   319.    2′-[5-(4-chlorophenyl)-2H-1,2,3,4-tetraazol-2-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   320. N-(5-isopropyl-1,3-thiazol-2-yl)-2-[5-(1-pyrrolidinyl)-2H-1, 2,    3, 4-tetraazol-2-yl]acetamide-   321.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-methyl-1-benzothiophen-2-yl)acetamide-   322.    N-(5-isopropyl-1,3-thiazol-2-yl)-4,4-bis(4-methylphenyl)-3-butenamide-   323. 2-cyclopropyl-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   324.    N-{4-bromo-6-[(5-isopropyl-1,3-thiazol-2-yl)amino]-6-oxohexyl}benzamide-   325. 2-cyclopentyl-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   326. benzyl    6-[(5-isopropyl-1,3-thiazol-2-yl)amino]-6-oxohexylcarbamate-   327.    N-1—(5-isopropyl-1,3-thiazol-2-yl)˜N˜4˜-(2-propynyl)-2-butenediamide-   328.    4-(2,4-dimethylphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-4-oxobutanamide-   329.    4-(4-benzyloxyphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-4-oxobutanamide-   330.    4-(thiphen-2-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)-4-oxobutanamide-   331. benzyl    2-{[(benzyloxy)carbonyl]amino}-5-[(5-isopropyl-1,3-thiazol-2-yl)amino]-5-oxopentanoate-   332.    4-(1H-indol-3-yl)-N-{3-[(5-isopropyl-1,3-thiazol-2-yl)amino]-3-oxopropyl}butanamide-   333. 4-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}phenyl    4-chlorobenzenesulfonate-   334.    N-(5-isopropyl-1,3-thiazol-2-yl)-4-{[(2-methoxyanilino)carbonyl]amino}benzamide-   335.    4-{[2-(isopropylsulfonyl)acetyl]amino}-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   336.    N-(5-isopropyl-1,3-thiazol-2-yl)-4-{[2-(phenylsulfanyl)acetyl]amino}benzamide-   337.    4-[(diethylamino)sulfonyl]-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   338. 2-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   339. 3,5-difluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   340.    3-{[(2-fluoroanilino)carbonyl]amino]-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   341.    N-(5-isopropyl-1,3-thiazol-2-yl)-1-phenyl-5-propyl-1H-pyrazole-4-carboxamide-   342.    3-chloro-4-(isopropylsulfonyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-5-(methylsulfanyl)-2-thiophenecarboxamide-   343.    3-iodo-4-(isopropylsulfonyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-5-(methylsulfanyl)-2-thiophenecarboxamide-   344.    2-{[(4-chlorophenyl)sulfonyl]methyl}-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methyl-1,3-thiazole-5-carboxamide-   345.    5-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-(trifluoromethyl)-3-furamide-   346.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,3,4,5,6-pentafluorophenyl)acetamide-   347. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-fluorophenyl)acetamide-   348. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-bromophenyl)acetamide-   349. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-chlorophenyl)acetamide-   350. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-nitrophenyl)acetamide-   351.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-trifluoromethylphenyl)acetamide-   352. N-(5-isopropyl-1,3-thiazol-2-yl)-2 (2-methoxyphenyl)acetamide-   353.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,5-dimethoxyphenyl)acetamide-   354.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,5-difluorophenyl)acetamide-   355. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4,5-trimethoxyphenyl)    acetamide-   356.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,6-dichlorophenyl)acetamide-   357.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-chloro-6-fluorophenyl)acetamide-   358.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,5-dimethoxyphenyl)acetamide-   359.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,5-difluorophenyl)acetamide-   360.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,5-bis-trifluoromethylphenyl)acetamide-   361.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methylthiophenyl)acetamide-   362. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methoxyphenyl)acetamide-   363. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-bromophenyl)acetamide-   364. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-chlorophenyl)acetamide-   365. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-fluorophenyl)acetamide-   366. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-nitrophenyl)acetamide-   367.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-trifluoromethylphenyl)acetamide-   368. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methylphenyl)acetamide-   369.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-dimethylaminophenyl)acetamide-   370.    2-[1,1′-biphenyl]-4-yl-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   371.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-trifluoromethylphenyl)acetamide-   372. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-bromophenyl)acetamide-   373. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-chlorophenyl)acetamide-   374. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-nitrophenyl)acetamide-   375. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-methoxyphenyl)acetamide-   376. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,4-dinitrophenyl)acetamide-   377.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,4-dichlorophenyl)acetamide-   378.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,4-difluorophenyl)acetamide-   379.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-benzyloxy-3-methoxyphenyl)acetamide-   380.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4-dichlorophenyl)acetamide-   381.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4-difluorophenyl)acetamide-   382.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4-dimethoxyphenyl)acetamide-   383.    2-(2,3-dihydro-1H-inden-5-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide-   384.    N-(5-isopropyl-1,3-thiazol-2-yl)-1-phenylcyclopropanecarboxamide-   385.    2-cyclopentyl-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide-   386. 2-cyclohexyl-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide-   387. N-(5-isopropyl-1,3-thiazol-2-yl)-2,2-diphenylacetamide-   388. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-nitrophenoxy)acetamide-   389. N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-nitrophenyl)propanamide-   390. N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl)propanamide-   391.    N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-isobutylphenyl)propanamide-   392. N-(5-isopropyl-1,3-thiazol-2-yl)-2-oxo-2-phenylacetamide-   393. N-(5-isopropyl-1,3-thiazol-2-yl)-3-methyl-2-phenylpentanamide-   394. (E, Z)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-2-butenamide-   395.    N-(5-isopropyl-1,3-thiazol-2-yl)bicyclo[4.2.0]octa-1,3,5-triene-7-carboxamide-   396. N-(5-isopropyl-1,3-thiazol-2-yl)-3-oxo-1-indanecarboxamide-   397. N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl)butanamide-   398. tert-butyl    (1S)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-1-methyl-2-oxoethylcarbamate-   399. tert-butyl    (1S,2S)-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-methylbutylcarbamate-   400. tert-butyl    2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate-   401. tert-butyl    (1S)-5-amino-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}pentylcarbamate-   402. tert-butyl    4-[(imino{[(4-methylphenyl)sulfonyl]amino}methyl)amino]-1-{[(5-isopropyl-1,3-thiazol-yl)amino]carbonyl}butylcarbamate-   403. tert-butyl    1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-3-(tritylamino)propylcarbamate-   404. tert-butyl    (1S)-1-(benzyloxymethyl)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate-   405. tert-butyl    (1S)-1-benzyl-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate-   406. tert-butyl    (1R)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-(benzylthiomethyl)ethylcarbamate-   407. benzyl    (3S)-3-[(tert-butoxycarbonyl)amino]-4-[(5-isopropyl-1,3-thiazol-2-yl)    amino]-4-oxobutanoate-   408. tert-butyl    (2S)-2-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-1-pyrrolidinecarboxylate-   409. tert-butyl    (1S)-1-(1H-indol-3-ylmethyl)-2-[(5-isopropyl-1,3-thiazol-2-yl)    amino]-2-oxoethylcarbamate-   410. tert-butyl    (1S)-1-([(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-3-(methylsulfanyl)propylcarbamate-   411. tert-butyl    (1S)-2-benzyloxy-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}propylcarbamate-   412. tert-butyl    (1S)-1-(4-benzyloxybenzyl)-2-[(5-isopropyl-1,3-thiazol-2-yl)    amino]-2-oxoethylcarbamate-   413. tert-butyl    (1S)-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-methylpropylcarbamate-   414. tert-butyl    (1S)-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-3-methylbutylcarbamate-   415. benzyl    (4S)-4-[(tert-butoxycarbonyl)amino]-5-[(5-isopropyl-1,3-thiazol-2-yl)amino]-5-oxopentanoate;    and the pharmaceutically acceptable salts thereof.

The compounds of formula (I) object of the present invention and thesalts thereof can be obtained, for instance, by a process comprisingreacting a compound of formula (II)

with a compound of formula (III)R₁—COX  (III)wherein R and R₁ are as defined above and X is hydroxy or a suitableleaving group;and, if desired, converting a 2-amino-1,3-thiazole derivative of formula(I) into another such derivative of formula (I), and/or into a saltthereof.

Examples of specific compounds of formula (III) wherein X is a suitableleaving group are those wherein X represents a halogen atom, preferablychlorine or bromine.

It is clear to the man skilled in the art that if the compound offormula (I), prepared according to the above process is obtained as anadmixture of isomers, its separation into the single isomers accordingto conventional techniques is still within the scope of the presentinvention. Likewise, the conversion into the free compound (I) of acorresponding salt thereof, according to well-known procedures in theart, is still within the scope of the invention.

The above process is an analogy process which can be carried outaccording to well known methods. The reaction between a compound offormula (II) and a carboxylic acid of formula (III) wherein X is ahydroxy group, can be carried out in the presence of a coupling agent ora polymer supported coupling agent such as, for instance, carbodiimide,i.e. 1,3-dicyclohexylcarbodiimide, 1,3-diisopropylcarbodiimide,1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, orN-Cyclohexylcarbodiimide N′-methylpolystyrene in a suitable solvent suchas, for instance, dichloromethane, chloroform, tetrahydrofuran, diethylether, 1,4-dioxane, acetonitrile, toluene, or N,N-dimethylformamide at atemperature ranging from about −10° C. to reflux for a suitable time,i.e. from about 30 min. to about 96 hours. The reaction between acompound of formula (II) and a compound of formula (III) can be alsocarried out, for example, by a mixed anhydride method, using an alkylchloroformate, such as ethyl, iso-butyl, or iso-propyl chloroformate, inthe presence of a tertiary base, such as triethylamine,N,N-diisopropylethylamine or pyridine, in a suitable solvent such as,for instance, toluene, dichloromethane, chloroform, tetrahydrofuran,acetonitrile, diethyl ether, 1,4-dioxane, or N,N-dimethylformamide, at atemperature ranging from about −30° C. to room temperature. The reactionbetween a compound of formula (II) and a carboxylic acid derivative offormula (III) wherein X is a suitable leaving group can be carried outin the presence of a tertiary base, such as triethylamine,N,N-diisopropylethylamine or pyridine, in a suitable solvent, such astoluene, dichloromethane, chloroform, diethyl ether, tetrahydrofuran,acetonitrile, or N,N-dimethylformamide, at a temperature ranging fromabout 10° C. to reflux.

Also the optional conversion of a compound of formula (I) into anothercompound of formula (I) can be carried out according to known methods.As an example, the nitro group of a compound of formula (I) may beconverted into an amino group by treatment, for example, with stannouschloride in concentrated hydrochloric acid and by using, if necessary,an organic solvent such as acetic acid, 1,4-dioxane and tetrahydrofuran,at a temperature varying between room temperature and about 100° C.Likewise, an alkylthio or an arylthio group may be converted into thecorresponding alkylsulfonyl and arylsulfonyl group by reaction, forexample, with mchloroperbenzoic acid in a suitable solvent such asdichloromethane or chloroform, at a temperature varying between about−5° C. and room temperature. The optional salification of a compound offormula (I) or the conversion of a salt into the free compound as wellas the separation of a mixture of isomers into the single isomers may becarried out by conventional methods.

The compounds of formula (II) and (III) according to the process objectof the present invention are known compounds or can be obtainedaccording to known methods.

For example, a compound of formula (II) wherein R is as defined abovecan be obtained by reacting a compound of formula (IV)

wherein Z is a bromine or chlorine atom, with thiourea in a suitablesolvent such as methanol, ethanol, tetrahydrofuran, 1,4-dioxane ortoluene, at a temperature varying between room temperature and reflux,for a suitable time ranging from about 1 hour to about 24 hours. Acompound of formula (III) wherein X is a leaving group as defined abovecan be obtained according to conventional techniques from thecorresponding carboxylic acids of formula (III) wherein X is hydroxy.When preparing the compounds of formula (I) according to the processobject of the present invention, optional functional groups within boththe starting materials or the intermediates thereof, which could giverise to unwanted side reactions, need to be properly protected accordingto conventional techniques. Likewise, the conversion of these latterinto the free deprotected compounds may be carried out according toknown procedures.Pharmacology

The compounds of formula (I) are active as cdk/cyclin inhibitors as theygave positive results when tested according to the following procedure.

The inhibiting activity of putative cdk/cyclin inhibitors and thepotency of selected compounds was determined through a method of assaybased on the use of the MultiScreen-PH 96 well plate (Millipore), inwhich a phosphocellulose filter paper was placed at each well bottomallowing binding of positive charged substrate after awashing/filtration step.

When a radioactivity labelled phosphate moiety was transferred by theser/threo kinase to the filter-bound histone, light emitted was measuredin a scintillation counter. The inhibition assay of cdk2/Cyclin Aactivity was performed according to the following protocol:

Kinase reaction: 1.5 μM histone H1 substrate, 25 μM ATP (0. 5 μCiP³³γ-ATP), 30 ng Cyclin A/cdk2 complex, 10 μM 10 inhibitor in a finalvolume of 100 μl buffer (TRIS HCl 10 mM pH 7.5, MgCl₂ 10 mM, 7.5 mM DTT)were added to each well of a 96 U bottom well plate. After 10 min at 37°C. incubation, reaction was stopped by 20 μl EDTA 120 mM.

Capture: 100 μl were transferred from each well to MultiScreen plate, toallow substrate binding to phosphocellulose filter. Plates were thenwashed 3 times with 150 μl/well PBS Ca⁺⁺/Mg⁺⁺ free and filtered byMultiScreen filtration system.

Detection: filters were allowed to dry at 37° C., then 100 μl/wellscintillant were added and ³³P labelled histone H1 was detected byradioactivity counting in the Top-Count instrument.

Results: data were analysed and expressed as % inhibition referred tototal activity of enzyme (=100%). All compounds showing inhibition ≧50%were further analysed in order to study and define potency (IC50) aswell as the kinetic-profile of inhibitor through Ki calculation.

IC50 determination: the protocol used was the same described above,where inhibitors were tested at concentrations ranging from 0.0045 to 10μM. Experimental data were analyzed by the computer program GraphPadPrizm.

Ki calculation: either the concentration of ATP and histone H1 substratewere varied: 4, 8, 12, 24, 48 μM for ATP (containing proportionallydiluted P¹³γ-ATP) and 0.4, 0.8, 1.2, 2.4, 4.8 μM for histone were usedin absence and presence of two different, properly chosen inhibitorconcentrations. Experimental data were analysed by the computer programSigmaPlot for Ki determination, using a random bireactant systemequation:

$v = \frac{V_{\max}\frac{(A)(B)}{{aK}_{A}K_{B}}}{1 + \frac{(A)}{K_{A}} + \frac{(B)}{K_{B}} + \frac{(A)(B)}{{aK}_{A}K_{B}}}$where A=ATP and B=histone H1.

Following the method above described, a representative compound offormula (I) of the invention, which is2-[4-(dimethylamino)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide,showed an inhibiting activity towards the cdk2/cyclin A complexcorresponding to 0.1 μM (Ki).

In addition, the inhibiting activity of putative cdk/cyclin inhibitorsand the potency of selected compounds was determined through a method ofassay based on the use of a SPA (Scintillation Proximity Assay) 96 wellplate assay. The assay is based on the ability of streptavidin coatedSPA beads to capture a biotinylated peptide derived from aphosphorylation site of histone. When a radioactivity labelled phosphatemoiety was transferred by the ser/threo kinase to the biotinylatedhistone peptide, light emitted was measured in a scintillation counter.The inhibition assay of cdk5/p25 activity was performed according to thefollowing protocol:

Kinase reaction: 1.0 μM biotinylated histone peptide substrate, 0.25 uCiP33g-ATP, 4 nM cdk2/p25 complex, 0–100 μM inhibitor in a final volume of100 μl buffer (Hepes 20 mM pH 7.5, MgCl2 15 mM, 1 mM DTT) were added toeach well of a 96 U bottom well plate. After 20 min at 37° C.incubation, the reaction was stopped by the addition of 500 ug SPA beadsin phosphate-buffered saline containing 0.1% Triton X-100, 50 uM ATP and5 mM EDTA. The beads were allowed to settle, and the radioactivityincorporated in the 33P-labelled peptide was detected in a Top Countscintillation counter.

Results: Data were analyzed and expressed as % Inhibition using theformula:100×(1−(Unknown−Bkgd)/(Enz. Control−Bkgd))

IC50 values were calculated using a variation of the four parameterlogistics equation:Y=100/[1+10^((LogEC50−X)*Slope)]Where X=log(uM) and Y % Inhibition.

The compounds of formula (I) are therefore useful to restrict theunregulated proliferation of tumor cells, hence in therapy in thetreatment of various tumors such as, for instance, carcinomas, e.g.mammary carcinoma, lung carcinoma, bladder carcinoma, colon carcinoma,ovary and endometrial tumors, sarcomas, e.g. soft tissue and bonesarcomas, and the hematological malignancies such as, e.g., leukemias.In addition, the compounds of formula (I) are also useful in thetreatment of other cell proliferative disorders such as psoriasis,vascular smooth cell proliferation associated with atherosclerosis andpost-surgical stenosis and restenosis and in the treatment ofAlzheimer's disease.

The compounds of the present invention can be administered either assingle agents or, alternatively, in combination with known anticancertreatments such as radiation therapy or chemotherapy regimen incombination with cytostatic or cytotoxic agents. As an example, theabove compounds can be administered in combination with one or morechemotherapeutic agents such as, for instance, taxane, taxanederivatives, CPT-11, camptothecin derivatives, anthracycline glycosides,e.g. doxorubicin or epirubicin, etoposide, navelbine, vinblastine,carboplatin, cisplatin and the like, optionally within liposomalformulations thereof.

The compounds of formula (I) of the present invention, suitable foradministration to a mammal, e.g. to humans, can be administered by theusual routes and the dosage level depends upon the age, weight,conditions of the patient and the administration route. For example, asuitable dosage adopted for oral administration of a compound of formula(I) may range from about 10 to about 500 mg pro dose, from 1 to 5 timesdaily.

The compounds of the invention can be administered in a variety ofdosage forms, e.g. orally, in the form of tablets, capsules, sugar orfilm coated tablets, liquid solutions or suspensions; rectally in theform of suppositories; parenterally, e.g. intramuscularly, or byintravenous and/or intrathecal and/or intraspinal injection or infusion.

The present invention also includes pharmaceutical compositionscomprising a compound of formula (I), or a pharmaceutically acceptablesalt thereof, in association with a pharmaceutically acceptableexcipient (which can be a carrier or a diluent). The pharmaceuticalcompositions containing the compounds of the invention are usuallyprepared following conventional methods and are administered in apharmaceutically suitable form.

For example, the solid oral forms may contain, together with the activecompound, diluents, e.g. lactose, dextrose, saccharose, sucrose,cellulose, corn starch or potato starch; lubricants, e.g. silica, talc,stearic acid, magnesium or calcium stearate, and/or polyethyleneglycols; binding agents, e.g. starches, arabic gum, gelatine,methylcellulose, carboxymethylcellulose or polyvinyl pyrrolidone;disaggregating agents, e.g. a starch, alginic acid, alginates or sodiumstarch glycolate; effervescing mixtures; dyestuffs; sweeteners; wettingagents such as lecithin, polysorbates, laurylsulphates; and, in general,non-toxic and pharmacologically inactive substances used inpharmaceutical formulations. Said pharmaceutical preparations may bemanufactured in known manner, for example, by means of mixing,granulating, tabletting, sugar-coating, or film-coating processes. Theliquid dispersions for oral administration may be e.g. syrups, emulsionsand suspensions. The syrups may contain as carrier, for example,saccharose or saccharose with glycerine and/or mannitol and/or sorbitol.The suspensions and the emulsions may contain as carrier, for example, anatural gum, agar, sodium alginate, pectin, methylcellulose,carboxymethylcellulose, or polyvinyl alcohol. The suspension orsolutions for intramuscular injections may contain, together with theactive compound, a pharmaceutically acceptable carrier, e.g. sterilewater, olive oil, ethyl oleate, glycols, e.g. propylene glycol, and, ifdesired, a suitable amount of lidocaine hydrochloride. The solutions forintravenous injections or infusions may contain as carrier, for example,sterile water or preferably they may be in the form of sterile, aqueous,isotonic saline solutions or they may contain as a carrier propyleneglycol. The suppositories may contain together with the active compounda pharmaceutically acceptable carrier, e.g. cocoa butter, polyethyleneglycol, a polyoxyethylene sorbitan fatty acid ester surfactant orlecithin.

The following examples illustrate but do not limit the presentinvention.

EXAMPLE 1 Preparation of Ethyl3-[(5-bromo-1,3-thiazol-2-yl)amino]-3-oxopropanoate

Ethyl malonyl chloride (0.88 ml; 6.99 mmol) was added to a mixture of2-amino-5-bromothiazole hydrobromide (1.30 g; 5.00 mmol) and Et3N (2.08ml; 14.94 mmol) in THF (6 ml) at 0–5° C. The mixture was stirred at roomtemperature overnight, then the reaction was quenched with potassiumsarcosinate (0.25 g; 2.00 mmol) and water (12 ml). The product wasisolated by filtration as a white solid (0.75 g, 51%): m.p. 165–166° C.

¹H-NMR (CDCl₃) δ ppm: 10.80 (bs, 1H, CONH); 7.38 (s, 1H, thiazole CH);4.28 (q, J=7.3 Hz, 2H, COOCH2CH3); 3.56 (s, 2H, COCH2CO); 1.32 (t, J=7.3Hz, 2H, COOCH2CH3).

Analogously, the following products can be prepared:

-   N-(5-bromo-1,3-thiazol-2-yl)-2-phenyl-acetamide

m.p. 206–207° C.

¹H.NMR (DMSO-D) δ ppm: 3.76 (s, 2H, COCH2Ph); 7.2–7.3 (m, 5H, Ph); 7.54(s, 1H, thiazole CH); 12.80 (bs, 1H, CONH);

-   N-(5-bromo-1,3-thiazol-2-yl)-benzamide

m.p. 126–128° C.

¹H-NMR (DMSO-d₆) δ ppm: 12.90 (bs, 1H, CONH); 8.07, 7.93 (m, 2H, o-Phhydrogens); 7.63 (s, 1H, thiazole CH); 7.62, 7.53, 7.48 (m, 3H, m- andp-Ph hydrogens);

-   Ethyl 4-[(5-bromo-1,3-thiazol-2-yl)amino]-4-oxobutanoate.

EXAMPLE 2 Preparation of N-(5-Bromo-thiazol-2-yl)-3-hydroxypropionamide

A mixture of LiBH4 (44 mg, 2.02 mmol), ethyl3-[(5-bromo-1,3-thiazol-2-yl)amino]-3-oxopropanoate (340 mg, 1.16 mmol),ethanol (0.082 ml, 2.02 mmol), and Et2O (50 ml) was refluxed for 20 min.The reaction was quenched with 1 N hydrochloric acid with ice-cooling.The mixture was then diluted with water and extracted withdichloromethane. The extract was dried and the solvent was evaporatedunder reduced pressure. Purification by silica gel chromatography(dichloromethane/methanol=98:2 and then 95:5) yielded the title compoundas a white solid (0.17 g; 52%).

m.p. 182–184° C. (dec.)

¹H-NMR (CDCl₃) δ ppm: 10.20 (bs, 1H, CONH); 7.35 (s, 1H, thiazole CH);4.04 (t, J=5.4 Hz, 2H, COCH2CH2OH); 2.74 (t, J=5.4 Hz, 2H, COCH2CH₂OH).

Analogously, starting from the corresponding ester derivative thefollowing product can be prepared:

-   N-(5-Bromo-1,3-thiazol-2-yl)-4-hydroxybutanamide.

EXAMPLE 3 Preparation of N-(5-Bromo-thiazol-2-yl)-2-ethoxy-acetamide

EDCI (0.53 g, 2.78 mmol) was added to a solution of ethoxyacetic acid(0.29 g, 2.78 mmol) in CH2Cl2 (5 ml) under ice-cooling. After stirringfor 1 h, a solution of 2-amino-5-bromothiazole hydrobromide (0.60 g,2.31 mmol) and diisopropylethylamine (0.40 ml, 2.34 mmol) in CH2Cl2 (5ml) was added dropwise, and the entire mixture was kept at 0° C. for 1h, then at room temperature overnight. The solution was evaporated andthe residue partitioned between ethyl acetate and water. The ethylacetate layer was further washed with water, 5% citric acid, water,saturated sodium bicarbonate, and water. Drying over sodium sulfate andevaporation gave a solid which was triturated with isopropyl ether togive the title compound as a beige solid (0.43 g; 70%)

m.p. 100–102° C.

¹H-NMR (CDCl₃) δ ppm: 9.64 (bs, 1H, CONH); 7.38 (s, 1H, thiazole CH);4.16 (s, 2H, COCH2O); 3.65 (q, J=6.8 Hz, 2H, OCH2CH3); 1.29 (t, J=6.8Hz, 3H, OCH2CH3).

Analogously, the following products can be prepared:

-   tert-butyl 3-[(5-bromo-1,3-thiazol-2-yl)amino]-3-oxopropylcarbamate;-   Benzyl 4-[(5-bromo-1,3-thiazol-2-yl)amino]-4-oxobutylcarbamate;-   tert-butyl    4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}phenylcarbamate-   tert-butyl    4-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}phenylcarbamate-   tert-butyl    4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-ylcarbamate;-   N-(5-bromo-1,3-thiazol-2-yl)-2-bromoacetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-bromoacetamide;-   2-N-[2-(3-pyridyl)-acetyl-amino]-5-bromo-thiazole

m.p. 232–235° C.

¹H-NMR (DMSO-d₆): 3.82 (s, 2H, COCH2Ph); 7.34 (dd, J=4.4, 7.7 Hz, 1H, H5Py); 7.55 (s, 1H, thiazole CH); 7.71 (ddd, J=1.6, 2.2, 7.7 Hz, 1H, H4Py); 8.45 (dd, J=1.6, 4.9 Hz, 1H, H6 Py); 8.49 (d, J=2.2 Hz, 1H, H2 Py);12.65 (s, 1H, CONH);

-   2-N-[2-(3-pyridyl)-acetyl-amino]-5-isopropyl-thiazole

m.p. 178–180° C. (dec.)

¹H-NMR (DMSO−d₆) δ ppm: 12.20 (bs, 1H, CONH); 8.45, 7.7, 7.35 (m, 4H,Py); 7.17 (s, 1H, thiazole CH); 3.78 (s, 2H, COCH2); 3.14 (m, 1H, CHMe₂); 1.22 (d, 6H, CHMe ₂);

-   N-(5-bromo-1,3-thiazol-2-yl)-2-(3-hydroxyphenyl) acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-hydroxyphenyl)acetamide

m.p. 206–208° C.

¹H-NMR (DMSO−d₆) δ ppm: 12.1 (bs, 1H, CONH); 9.34 (s, 1H, OH); 7.14 (s,1H, thiazole CH); 7.1 (t, 1H, H5 Ph); 6.6—6.7 (m, 3H, 2H, h4, H6, Ph);3.6 (s, 2H, COH₂); 3.08 (ept, 1H CHMe₂); 1.22 (d, 6H, CHMe ₂);

-   N-(5-bromo-1,3-thiazol-2-yl)-2-(3-methoxyphenyl) acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-methoxyphenyl)acetamide

m.p. 97–98° C.

¹H-NMR (DMSO−d₆) δ ppm: 12.12 (s, 1H, CONH); 7.21 (dd, 1H, H5 Ph); 7.14(d, 1H, thiazole CH); 6.87 (m, 2H, H2, H6 Ph); 6.81 (ddd, 1H, H4 Ph);3.72 (s, 3H, OMe); 3.67 (s, 2H, COCH₂); 3.07 (m, 1H, CHMe₂); 1.22 (d,6H, CHMe ₂);

-   N-(5-bromo-1,3-thiazol-2-yl)-2-(3-chorophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-chorophenyl)acetamide

m.p. 116–118° C.

¹H-NMR (CDCl₃) δ ppm: 11.8 (bs, 1H, CONH); 7.32 (s, 1H, H2 Ph); 7.24 (m,3H, H4, H5, H6 Ph); 7.04 (s, 1H, thiazole CH); 3.76 (s, 2H, COCH₂); 3.13(m, 1H, CHMe₂); 1.31 (d, 6H, CHMe ₂);

-   N-(5-bromo-1,3-thiazol-2-yl)-2-(4-hydroxyphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-hydroxyphenyl)acetamide

¹H-NMR (DMSO-d₆) δ ppm: 12.07 (bs, 1H, CONH); 9.33 (sb, 1H, OH);7.17–6.7 (m, 5H, Ar+ CHthiazole); 3.60 (s, 2H, COCH₂) 3.1 (m, 1H,CHMe₂); 1.23 (d, 6H, CHMe ₂)

-   N-(5-bromo-1,3-thiazol-2-yl)-2-(3,4-dihydroxyphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4-dihydroxyphenyl)acetamide

m.p. 168–169° C.

¹H-NMR (DMSO-d₆) δ ppm: 12.01 (bs, 1H, CONH); 8.79 (sb, 2H, 2 OH); 7.12(s, 1H, thiazole CH); 6.69 (d, 1H, H2 Ph); 6.63 (d, 1H, H5 Ph); 6.52(dd, 1H, H6 Ph); 3.48 (s, 2H, COCH₂) 3.06 (m, 1H, CHMe₂); 1.22 (d, 6H,CHMe ₂);

-   N-(5-bromo-1,3-thiazol-2-yl)-2-(4-hydroxy-3-methoxyphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-hydroxy-3-methoxyphenyl)acetamide

m.p. 115–116° C.

¹H-NMR (DMSO-d₆) δ ppm: 12.0 (bs, 1H, CONH); 8.80 (s, 1H, OH); 7.12 (d,1H, thiazole CH); 6.88 (s, 1H, H2 Ph); 6.68 (m, 2H, H5, H6 Ph); 3.73 (s,3H, OMe); 3.56 (s, 2H, COCH₂) 3.07 (m, 1H, CHMe₂); 1.22 (d, 6H, CHMe ₂)

-   N-(5-bromo-1,3-thiazol-2-yl)-2-(4-methoxyphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methoxyphenyl)acetamide

m.p. 129–130° C.

¹H-NMR (DMSO-d₆) δ ppm: 12.08 (s, 1H, CONH); 7.21 (dd, 2H, H2, H6 Ph);7.13 (d, 1H, thiazole CH); 6.87 (dd, 2H, H3, H5 Ph); 3.70 (s, 3H, OMe);3.62 (s, 2H, COCH); 3.06 (m, 1H, CHMe₂); 1.22 (d, 6H, CHMe ₂);

-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-acetamide

m.p. 135–137° C.

¹H-NMR (DMSO-d₆) δ ppm: 12.20 (bs, 1H, CONH); 7.29 (m, 5H, Ph); 7.13 (s,1H, thiazole CH); 3.70 (s, 2H, COCH₂); 3.07 (m, 1H, CHMe₂); 1.22 (d, 6H,CHMe ₂);

-   2-[3-(3-chloropropoxy)pheny]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide

m.p. 91–92° C.

¹H-NMR (DMSO-d₆) δ ppm: 12.08 (bs, 1H, CONH); 7.21 (t, 1H, H5 Ph); 7.13(s, 1H, thiazole CH); 6.8–6.9 (m, 3H, H2, H4, H6 Ph); 4.05 (t, 2H, OCH₂CH₂CH₂Cl); 3.77 (t, 2H, OCH₂CH₂CH₂Cl) 3.67 (s, 2H, COCH₂); 3.07 (ept,1H, CHMe₂); 2.14 (quint, 2H, OCH₂CH₂CH₂Cl); 1.22 (d, 6H, CHMe ₂); and

-   2-[3-(2-chloroethoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide

m.p. 134–135° C.

¹H-NMR (DMSO-d₆) δ ppm: 12.09 (bs, 1H, CONH); 7.22 (t, 1H, H5 Ph); 7.13(s, 1H, thiazole CH); 6.8–6.9 (m, 3H, H2, H4, H6 Ph); 4.2 (t, 2H, OCH₁CH₂Cl); 3.91 (t, 2H, OCH₂CH₂Cl); 3.67 (s, 2H, COCH₂); 3.07 (ept, 1H,CHMe₂); 1.22 (d, 6H, CHMe ₂)

EXAMPLE 4 Preparation of N-(5-bromo-thiazol-2-yl)-4-sulfamoylbenzamide

To a mixture of 4-sulfamoylbenzoic acid (1.0 g, 4.97 mmol), Et3N (1.5ml, 10.78 mmol), DMF (5 ml) and THF (5 ml) isobutyl choroformate (0.70ml, 5.36 mmol) was added dropwise at −10° C. After stirring for 1 h, asolution of 2-amino-5-bromothiazole hydrobromide (1,55 g, 5.96=mol) andEt3N (0.83 ml, 5.96 mmol) in DMF (6 ml) and THF (4 ml) was addeddropwise to the mixture at the same temperature.

The resulting mixture was gradually warmed to room temperature over aperiod of 3 h and then concentrated by evaporation of the solvent invacuo. To the resultant residue AcOEt and 5% aqueous NaHCO3 were added.The separated organic phase was washed with water, dried over anhydrousNa2SO4, and concentrated under reduced pressure. The residual solid waspurified by flash cromatography (dichloromethane/methanol/30% aqueousammonia=95:5:0.5) to afford the title compound as a yellow solid (0.77g, 43%)

m.p. 268–270° C.

¹H-NMR (DMSO-d) δ ppm: 7.54 (s, 2H, SO2NH2); 7.67 (s, 1H, thiazole CH);7.94 (d, J=8.8 Hz, 2H, H3 and H5 Ph); 8.21 (d, J=8.8 Hz, 2H, H2 and H6Ph); 13.10 (bs, 1H, CONH).

Analogously, the following product can be prepared:

-   N-(5-isopropyl-thiazol-2-yl)-4-sulfamoyl-benzamide

m.p. 222–224° C.

¹H-NMR (DMSO-d₆) δ ppm: 12.65 (bs, 1H, CONH); 8.18 (dd, 2H, H2, H6 Ph);7.92 (dd, 2H, H3, H5 Ph); 7.51 (s, 2H, SO₂NH₂); 7.25 (s, 1H, thiazoleCH); 3.13 (m, 1H, CHMe₂); 1.28 (d, 6H, CHMe ₂).

EXAMPLE 5 Preparation of 4-amino-N-(5-bromo-1,3-thiazol-2-yl)butanamidehydrobromide

A solution (1.3 ml) of hydrogen bromide in glacial acetic acid (33%) wasadded to benzyl 4-[(5-bromo-1,3-thiazol-2-yl)amino]-3-oxobutylcarbamate(0.72 g, 1.81 mmol) and the mixture was stirred at room temperature for1 h.

Ether was added and the solid was filtered and washed with ether. Thecrude product was recrystallized from MeOH/ether to afford the titlecompound as a beige solid (0.38 g, 61%), m.p. 211–213° C. (dec.)

¹H-NMR (DMSO-d₆) δ ppm: 1.84 (m, 2H, COCH2CH2CH2NH2); 2.53 (t, J=6.8 Hz,2H, COCH2CH2CH2NH2); 2.81 (m, 2H, COCH2CH2CH2NH2); 7.68 (bs, 3H, NH3+);12.42 (s, 1H, CONH)

EXAMPLE 6 Preparation of3-amino-N-(5-bromo-1,3-thiazol-2-yl)propionamide hydrochloride

A solution 3.6 N HCl in isopropanol (14 ml) was added to tert-butyl3-[(5-bromo-1,3-thiazol-2-yl)amino]-4-oxopropylcarbamte (0.90 g, 2.57mmol) and the mixture was stirred at room temperature overnight. Thesolvent was evaporated and the residual solid was triturated in ether,filtered and dried in vacuo to afford the title compound as a whitesolid (0.73 g, quantitative yield)

m.p. 255° C. ca.(dec.)

¹H-NMR (DMSO-d₆) δ ppm: 2.83 (t, J=6.8 Hz, 2H, COCH ₂CH₂NH₂); 3.07 (q,J=6.4 Hz, 2H, COOH₂CH ₂NH₂); 7.55 (s, 1H, thiazole CH); 7.96 (bs, 3H,NH3+); 12.58 (s, 1H, CONH).

Analogously, the following compounds can be prepared:

-   2-(4-aminophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide

¹H-NMR (DMSO-d₆) δ ppm: 1.22 (d, 6H, CHMe ₂); 3.07 (m, 1H, CHMe₂); 3.47(s, 2H, COCH₂); 4.94 (s, 2H, NH₂); 6.48 (m, 2H, H3, H5 Ph); 6.93 (m, 2H,H2, H6 Ph); 7.12 (d, 1H, CH thiazole); 12.00 (s, 1H, CONH).

-   4-amino-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide

¹H-NMR (DMSO-d₆) δ ppm: 1.29 (d, 6H, CHMe ₂); 3.12 (m, 1H, CHMe₂); 6.58(m, 2H, H3, H5 Ph); 7.18 (d, 1H, CH thiazole) 7.82 (m, 2H, H2, H6 Ph);12.80 (bs, 1H, CONH).

-   2-(2-amino-1,3-thiazol-4-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide

m.p. 204–206° C. ca.(dec.)

¹H-NMR (DMSO-d₆) δ ppm: 1.24 (d, 6H, CHMe ₂); 3.10 (m, 1H, CHMe₂); 3.54(s, 2H, COCH₂); 6.30 (s, 1H, H5 thiazole); 6.88 (s, 2h, NH₂); 7.13 (s,1H, H4 thiazole); 11.90 (s, 1H, ONH).

EXAMPLE 7 Preparation of N-(5-isopropyl-1,3-thiazol-2-yl)-butanamide

Triethylamine (0.97 ml; 6.34 mmol) and butanoyl chloride (0.52 ml; 5.07mmol) were added in this order to a solution of2-amino-5-isopropyl-1,3-thiazole (0.6 g; 4.23 mmol) in dichloromethane(8 ml), cooled to −5° C. The reaction mixture was stirred at −5° C. for2 hours and then warmed to room temperature. After additional 4 hours,the organic layer was washed with water, saturated sodium bicarbonate,1N hydrochloric acid, brine, dried over sodium sulfate and evaporated.The residue was recrystallized from cyclohexane to yield 0.45 g (50%) ofthe title compound as a colourless solid (m.p. 95–97° C.)

¹H-NMR (DMSO-d₆) δ ppm: 11.82 (s, 1H, CONH); 7.11 (s, 1H, thiazole CH);3.08 (m, 1H, CHMe2); 2.34 (t, J=7.1 Hz, 2H, COCH2CH2CH3); 1.58 (m, 2H,COCH2CH2CH3); 1.23 (d, J=6.6 Hz, 6H, (CH3)₂CH); 0.87 (t, J=7.1 Hz, 3H,COCH2CH2CH3).

Analogously, the following compounds can be prepared:

-   N-(5-bromo-1,3-thiazol-2-yl)-butanamide

m.p. 163–164° C.

¹H-NMR (DMSO-d₆) δ ppm: 12.27 (bs, 1H, CONH); 7.50 (s, 1H, thiazole CH);2.39 (t, 2H, COCH2CH2CH3); 1.59 (m, 2H, COCH2CH2CH3); 0.87 (t, 3H,COCH2CH2CH3);

-   N-(5-chloro-1,3-thiazol-2-yl)-butanamide

m.p. 170–171° C.

¹H-NMR (DMSO-d₆) δ ppm: 12.25 (bs, 1H, CONH); 7.46 (s, 1H, thiazole CH);2.38 (t, 2H, COCH2CH2CH3); 1.59 (m, 2H, COCH2CH2CH3); 0.87 (t, 3H,COCH2CH2CH3);

-   N-(5-phenyl-1,3-thiazol-2-yl)-butanamide

m.p. 183–184° C.

¹H-NMR (DMSO-d₆) δ ppm: 12.13 (s, 1H, CONH), 7.84 (s, 1H, thiazole CH);7.58 (d, J=6.8 Hz, 2H, o-Ph hydrogens); 7.39 (dd, J 6.8 and 7.8 Hz, 2H,m-Ph hydrogens); 7.28 (t, J=7.8 Hz, 1H, p-Ph hydrogens); 2.41 (t, J=7.3Hz, 2H, COCH2CH2CH3); 1.61 (m, 2H, COCH2CH2CH3); 0.89 (t, J=7.3 Hz, 3H,COCH2CH2CH3);

-   N-(5-nitro-1,3-thiazol-2-yl)-butanamide

m.p. 175–176° C.

¹H-NMR (DMSO-d₆) δ ppm: 13.02 (s, 1H, CONH); 8.60 (s, 1H, thiazole CH);2.48 (t, J=7.3 Hz, 2H, COCH2CH2CH3); 1.62 (m, 2H, COCH2CH2CH3); 0.89 (t,J=7.3 Hz, 3H, COCH2CH2CH3);

-   N-(5-methyl-1,3-thiazol-2-yl)-butanamide

m.p. 137–138° C.

¹H-NMR (CDCl₃) δ ppm: 11.89 (s, 1H, CONH); 7.04 (s, 1H, thiazole CH);2.48 (t, J=7.3 Hz, 2H, COCH2CHCH3); 2.41 (s, 3H, CH3); 1.80 (m, 2H,COCH2CH2CH3); 1.02 (t, J=7.3 Hz, 3H, COCH2CH2CH3);

-   N-(5-benzyl-1,3-thiazol-2-yl)-butanamide

m.p. 147–149° C.

¹H-NMR (CDCl₃) δ ppm: 7.23 (m, 5H, Ph); 7.07 (s, 1H, thiazole CH); 4.08(s, 2H, CH2Ph); 2.45 (t, J=7.8 Hz, 2H, COCH2CH2CH3); 1.76 (m, 2H,COCH2CH2CH3); 0.97 (t, J=7.8 Hz, 2H, COCH2CH2CH3);

-   N-(5-isobutyl-1,3-thiazol-2-yl)-butanamide

m.p. 58–60° C.

¹H-NMR (CDCl₃) δ ppm: 7.03 (s, 1H, thiazole CH); 2.61 (d, J=7.3 Hz, 2H,Me2CHCH2); 2.45 (t, J=7.8 Hz, 2H, COCH2CH2CH3); 1.81 (m, 1H, Me2CHCH2);1.78 (m, 2H, COCH2CH2CH3); 1.01 (t, J=7.8 Hz, 3H, COCH2CH2CH3); 0.95,0.93 (s, 6H, Me2CHCH2);

-   N-(5-cyclopropyl-1,3-thiazol-2-yl)-butanamide;-   N-{5-[2-(methylsulfonyl)ethyl]-1,3-thiazol-2-yl}-butanamide

m.p. 153–155° C.

¹H-NMR (CDCl₃) δ ppm: 11.01 (s, 1H, CONH); 7.21 (s, 1H, thiazole CH);3.34 (m, 4H, CH3SO2CH2CH2); 2.90 (s, 3H, H3SO₂); 2.48 (t, J=7.3 Hz, 2H,COCH2CH2CH3); 1.80 (m, H, COCH2CH2CH3); 1.02 (t, J=7.3 Hz, 3H,COCH2CH2CH3);

-   N-[5-(2-methylthioethyl)-1,3-thiazol-2-yl]-butanamide-   m.p. 67–69° C.

¹H-NMR (CDCl₃) δ ppm: 11.63 (bs, 1H, NHCO), 7.26 (s, 1H, thiazole CH),3.06 (t, J=7.0 Hz, 2H, CH3SCH2CH2); 2.77 (t, J=7.0 Hz, 2H, CH3SCH2CH2);2.48 (t, J=7.3 Hz, 2H, COCH2CH2CH3); 2.14 (s, 3H, CH3S); 1.80 (m, 2H,COCH2CH2CH3); 1.02 (t, J=7.3 Hz, 3H, COCH2CH2CH3);

-   N-{5-[2-(methoxycarbonyl)ethyl]-1,3-thiazol-2-yl}-butanamide;-   N-[5-(3-methoxy-propyl)-1,3-thiazol-2-yl]-butanamide

m.p. 80–82° C.

¹H-NMR (CDCl₃) δ ppm: 11 (sb, 1H, NHCO); 7.07 (s, 1H, H4 thiazole); 3.41(t, 2H, CH₂CH₂CH₂OMe); 3.34 (s 3H, OCH₃); 2.85 (t, 2H, CH₂CH₂CH₂OMe);2.46 (t, 2H, NHCOCH₂); 1.91 (m, 2H, CH₂CH₂CH₂OMe); 1.80 (t, 2H.NHCOCH₂CH₂CH₃); 1.01 (t, 3H, NHCOCH₂CH₂CH₃);

-   N-[5-(2-ethoxy-ethyl)-1,3-thiazol-2-yl]-butanamide

m.p. 74–76° C.

¹H-NMR (CDCl₃) δ ppm: 7.14 (s, 1H, H4 thiazole); 3.64 (t, 2H,CH₂CH₂OEt); 3.52 (q 2H, OCH₂CH₃); 3.02 (t, 2H, CH₂CH₂OEt); 2.47 (t, 2H,NHCOCH₂); 1.80 (m, 2H, NHCOCH₂CH₂); 1.23 (t, 3H. OCH₂CH₃); 1.02 (t, 3H,NHCOCH₂CH₂CH₃);

-   N-[5-(indol-3-yl-methyl)-1,3-thiazol-2-yl]-butanamide

m.p. 240–242° C.

¹H-NMR (CDCl₃) δ ppm: 9.95 (bs, 1H, CONH); 8.00 (bs, 1H, NH indole);7.54 (d, 1H, H4 indole); 7.36 (d, 1H, H7 indole); 7.19 (m, 1H, H6indole); 7.17 (s, 1H, thiazole CH); 7.09 (m, 1H, H5 indole); 7.07 (s,1H, H2 indole); 4.23 (s, 2H, CH₂); 2.39 (m 2H, CH₂CO); 1.73 (m, 2H,CH₂CH ₂CH₂); 0.96 (t, 3H, CH ₃CH₂CH₂).

-   N-[5-(3-dimethylaminoimino-butyl)-1,3-thiazol-2-yl]butanamide.

EXAMPLE 8 2-amino-5-isopropyl-1,3-thiazole

2 ml (18.6 mmol) of 3-methylbutyraldehyde were dissolved in 15 ml ofdioxane. 40.4 ml (18.6 mmol) of a solution 2% v/v of bromine in dioxanewas dropped therein at 0° C. The mixture was maintained at roomtemperature under stirring for 2 hours, then 2.83 g (37.2 mmol) ofthiourea and 5 ml of ethanol were added. After 6 hours at roomtemperature the solution was evaporated to dryness, the residue wasdissolved in methylene chloride and the product extracted with 1Mhydrochloric acid; the aqueous layer was made basic by using 30%ammonium hydrate and extracted again with methylene chloride. Theorganic phase was dried over sodium sulfate and evaporated under vacuum.The residue was chromatographed on a silica gel column, eluting withcyclohexane-ethylacetate to give 1.1 g (42% yield) of the titlecompound.

¹H-NMR (DMSO-D₆) δ ppm: 6.6 (s, 2H, NH2); 6.58 (s, 1H, thiazole CH); 2.9(m, 1H, CHMe2); 1.18 (s, 3H, MeCHMe); 1.17 (s, 3H, MeCHMe).

Analogously the following products can be prepared starting from thesuitable aldehyde:

-   2-amino-5-isobutyl-1,3-thiazole

¹H-NMR (DMSO-d₆) δ ppm: 6.61 (sb, 2H, NH2); 6.56 (s, 1H, thiazole CH);2.39 (dd, 2H, CH₂CHMe₂); 1.65 (m, 1H, CHMe₂); 0.85 (d, 6H, CHMe ₂);

-   2-amino-5-phenyl-1,3-thiazole;-   2-amino-5-benzyl-1,3-thiazole;

¹H-NMR (DMSO-d₆) δ ppm: 7.3–7.2 (m, 5H, Ph); 6.68 (s, 1H, thiazole CH);6.67 (sb, 2H, NH2); 3.87 (s, 2H, CH₂Ph)

-   2-amino-5-(3-indolylmethyl)-1,3-thiazole;-   2-amino-5-ethoxyethyl-1,3-thiazole;-   2-amino-5-methoxypropyl-1,3-thiazole;-   2-amino-5-cyclopropyl-1,3-thiazole;-   2-amino-5-methylthioethyl-1,3-thiazole;-   2-amino-5-formyl-1,3-thiazole;-   2-amino-5-(3-dimethylaminoimino)butyl-1,3-thiazole.

EXAMPLE 9 4-ethoxy-1-butanol

85 mg (0.004 mmol) of sodium were dissolved in 50 ml of methanol and 8.7g (0.23 mol) of sodium borohydride were added. A solution of 4.6 g(0.032 mol) of methyl 4-ethoxybutanoate in 20 ml of methanol was droppedto the mixture under stirring. The reaction is maintained at reflux for6 hours, then 300 ml of brine were added and the product was extractedwith methylene chloride. The organic layer was dried over anhydroussodium sulfate and evaporated to dryness to give 2.25 g (61% yield) ofthe title compound.

Analogously the following products can be prepared starting from thesuitable ester:

-   2-cyclopropyl-1-ethanol;-   3-(3-indolyl)-1-propanol; and-   5-dimethylaminoimino-1-hexanol.

EXAMPLE 10 Methyl 3-(3-indolyl)-propanoate

2 g (10.57 mmol) of 3-indolepropionic acid were dissolved in 50 ml ofmethanol. The solution was cooled to 0° C. and 5 ml of sulfuric acid 96%were dropped under stirring. The solution was maintained at roomtemperature overnight and then poured onto ice-water, basified with 30%ammonium hydrate and finally extracted with methylene chloride. Theorganic layer was dried over anhydrous sodium sulfate and evaporated todryness to give 2.3 g of an oily product (93% yield).

Analogously the following products can be prepared starting 35 from thesuitable carboxylic acid:

-   Methyl 4-ethoxy butanoate;-   Methyl cyclopropylacetate; and-   5-methoxycarbonylethyl-2-amino-1,3-thiazole.

EXAMPLE 11 4-methyl-pentanal

1.24 ml (14.18 mmol) of oxalyl chloride were dissolved in 10 ml ofmethylene chloride and after cooling to −60° C., 2.31 ml of DMSO (35mmoles) were dropped. After 5 minutes at the same temperature, asolution of 1 ml (11.9 mmol) of 4-methyl-1-pentanol in 10 ml ofmethylene chloride was slowly dropped. The mixture was maintained understirring for 30 minutes at the same temperature, then 8.3 ml (59.5 mmol)of triethylamine were added. After 2 hours at 0° C. water was added. Themixture was diluted with methylene chloride and washed successively with1M hydrochloric acid, water, saturated sodium bicarbonate and finallywith brine. The organic layer was dried over anhydrous sodium sulfateand evaporated to dryness to give 0.7 g (25% yield) of the titlecompound.

Analogously the following products can be prepared starting from thesuitable alcohol:

-   2-cyclopropyl-1-ethanal;-   4-methylthio-1-butanal;-   4-ethoxy-1-butanal;-   5-methoxy-1-pentanal; and-   5-dimethylaminoimino-1-hexanal.

EXAMPLE 12 5-benzyloxy-1-methoxy-pentane

1.6 g (0.039 mol) of 55% sodium hydride in oil were added to 50 ml ofdimethylformamide under stirring at room temperature. 5 ml (0.026 mol)of 5-benzyloxy-1-pentanol and 2.43 ml (0.039 mol) of methyl iodide werethen added successively. After a night the excess of sodium hydride wasdecomposed with water and the solvent evaporated under vacuum. Theresidue was redissolved with methylene chloride and washed with water.The organic layer was finally dried over anhydrous sodium sulfate andevaporated to give 3.5 g (70% yield) of the title compound.

Analogously, by using ethyl iodide, the following compound can beprepared:

-   4-ethoxy-butanoic acid.

EXAMPLE 13 5-methoxy-1-pentanol

3.5 g (0.018 mol) of 5-benzyloxy-1-methoxy-pentane were dissolved in 50ml of ethanol and 400 mg of 10% palladium on activated charcoal wereadded. The mixture was hydrogenated at 40 psi at room temperature for 5hours, then filtered on celite and evaporated under vacuum to give 1.77g (84% yield) of the title compound.

EXAMPLE 14 15 Ethyl 5-dimethylaminoimino-hexanoate

15.8 g (100 mmol) of ethyl 4-acetyl-butanoate and 6 g (100 mmol) ofanhydrous N,N-dimethyl hydrazine in 50 ml of toluene containing 0.1 mlof trifluoroacetic acid were heated at 70° C. for 5 hours. The mixturewas then washed 20 with water, dried over anhydrous sodium sulfate andevaporated to give 12.3 g (79% yield) of the title compound.

EXAMPLE 15 25 N-[5-(3-oxo-butyl)-1,3-thiazol-2-yl]-butanamide

To a stirred solution of 200 mg (1 mmol) of cupric acetate in 10 ml ofwater 141 mg (0.5 mmol) ofN-[5-(3-dimethylaminoimino-butyl)-1,3-thiazol-2-yl]-butanamide in 10 mlof tetrahydrofuran were added. After 2 hours the solvent was removedunder reduced pressure, a mixture of aqueous ammonium chloride andammonium hydroxide was added and the product extracted with methylenechloride to give after drying and concentration 114 mg (95% yield) ofthe title compound.

EXAMPLE 16 2-benzyloxycarbonylamino-5-formyl-1,3-thiazole

1 g (7.8 mmol) of 2-amino-5-formyl-1,3-thiazole was dissolved in 25 mlof tetrahydrofuran and 1.35 ml (9.36mmol) of triethylamine and 1.33 ml(9.36 mmol) of benzylchloroformate were added at 0° C. under stirring.After 8 hours at room temperature the solvent was evaporated, theresidue redissolved with methylene chloride and washed with saturatedtartaric acid and then with water. The solvent was dried over anhydroussodium sulfate and evaporated. The residue was purified bychromatography on silica gel using cyclohexane-ethylacetate as eluent togive 1.3 g (65% yield) of the title compound.

EXAMPLE 17 5-hydroxymethyl-2-benzyloxycarbonylamino-1,3-thiazole

530 mg (14 mmol) of sodium borohydride were added in small portions to astirred solution of 7 g (27 mmol) of2-benzyloxycarbonylamino-5-formyl-1,3-thiazole in 80 ml of methanol atroom temperature. The reaction went on for 2 hours. After evaporation ofthe solvent the residue was purified by chromatography(cyclohexane-ethylacetate) to give 5.05 g (71% yield) of the titlecompound.

EXAMPLE 182-benzyloxycarbonylamino-5-(4-phenyl-1-sulfonyloxy)methyl-1,3-thiazole

To a solution of 1 g (3.78 mmol) of2-benzyloxycarbonylamino-5-hydroxymethyl-1,3-thiazole in 25 ml ofpyridine 0.86 g (4.54 mmol) of tosyl chloride in 10 ml of pyridine weredropped at 0° C. After stirring at room temperature for 6 hours thesolvent was evaporated under vacuum, the residue redissolved withmethylene chloride, washed with 1M hydrochloric acid and finally withwater.

The organic layer was dried over anhydrous sodium sulfate andevaporated. The residue was purified by chromatography on silica gel(cyclohexane-ethylacetate) to give 1.2 g (80% yield) of the titlecompound.

EXAMPLE 192-benzyloxycarbonylamino-5-(2-ethoxycarbonyl-3-ethoxycarbonylethyl)-1,3-thiazole

To a suspension of 321 mg of 55% sodium hydride in oil (7.4 mmol) in 20ml of tetrahydrofuran 1.12 ml (7.4 mmol) of diethylmalonate were added.After 30 minutes, a solution of 1.5 g (3.7 mmol) of2-benzyloxycarbonylamino-5-(4-phenyl-1-sulphonyloxy)methyl-1,3-thiazolein 10 ml of the same solvent was dropped under stirring. After 6 hoursthe solvent was evaporated and the residue redissolved with methylenechloride and washed with water. The organic layer was dried overanhydrous sodium sulfate and evaporated. The residue was chromatographedon a silica gel column (cyclohexane-ethylacetate) to give 1.05 g (70%yield) of the title compound.

EXAMPLE 20 2-benzyloxycarbonylamino-5-ethoxycarbonylethyl-1,3-thiazole

To a solution of 4.06 g (10 mmol) of2-benzyloxycarbonylamino-5-(2-ethoxycarbonyl-3-ethoxycarbonylethyl)-1,3-thiazolein 10 ml of dimethylsulphoxide 0.64 g (11 mmol) of sodium chloride and0.36 (20 mmol) of water were added under stirring. The mixture washeated at 160° C. for 8 hours and then the solvent removed under vacuum.The residue was redissolved with methylene chloride and washed withbrine. After drying and concentration the residue was chromatographed ona silica gel column (cyclohexane-ethylacetate) to give 2.67 g (80%yield) of the title compound.

EXAMPLE 21 2-amino-5-carboxyethyl-1,3-thiazole

1 g (2.9 mmol) of2-benzyloxycarbonylamino-5-ethoxycarbonylethyl-1,3-thiazole wasdissolved in 20 ml of 33% hydrobromic acid in acetic acid. After 2 hoursat room temperature, the solvent was evaporated under vacuum. Theresidue was redissolved in the minimum amount of water and thehydrobromide of the title compound was precipitated by addingdiethylether (75% yield).

EXAMPLE 22 Preparation of methyl 2-[3-(3-chloropropoxy)phenyl]acetate

A mixture of methyl (m-hydroxyphenyl)acetate ((5 g, 0.03 moles),1-bromo-3-chloropropane (3.26 ml, 0.03 moles) and anhydrous potassiumcarbonate (6.4 g) in anhydrous acetone (60 ml) was refluxed for 40hours. After cooling, the precipitate was filtered off and the solutionwas evaporated to dryness to give the product as an oil, which waspurified by flash chromatography with hexane:AcOEt (97:3) as eluent (6.2g, 85% yield).

Analogously, the following product can be prepared:

-   methyl 2-[3-(2-chloroethoxy)phenyl]acetate.

EXAMPLE 23 Preparation of 2-[3-(3-chloropropoxy)phenyl]acetic acid

A mixture of methyl 2-[3-(3-chloropropoxy)phenyl]acetate (4.95 g, 0.02moles) and a solution of 1N sodium hydroxide (0.02 moles) was stirred atroom temperature for 24 hours. After acidification the acid separated aswhite powder (4.53 g, 97% yield)

m.p. 83–84° C.

Analogously, the following product can be prepared:

-   2-[3-(2-chloroethoxy)phenyl]acetic acid

m.p. 100–101° C.

EXAMPLE 24 Preparation ofN-(5-isopropyl-1,3-thiazol-2-yl)-2-{3-[3-(4-morpholinyl)propoxy]phenyl}acetamide

A mixture of2-[3-(3-chloropropoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide(1.00 g, 2.8 mmoles), morpholine (1.24 ml, 14.2 mmoles), potassiumiodide (0.24 g, 1.4 mmoles) in anhydrous dimethylformamide (3.5 ml) washeated at 100° C. for 6 hours. The solution was acidified and extractedwith ether to eliminate unreacted products; then the solution wasbasified and extracted with ether. The solvent was evaporated to drynessto give the product as an oily semisolid which was purified by flashchromatography with dichloromethane:methanol (97:3) as eluent (1.0 g,87% yield)

¹H-NMR (DMSO-d₆) δ ppm: 12.09 (bs, 1H, CONH); 7.21 (t, 1H, H5 Ph); 7.13(s, 1H, thiazole CH); 6.8–6.9 (m, 3H, H2, H4, H6 Ph); 3.97 (t, 2H, OCH₂CH₂CH₂N); 3.66 (s, 2H, COCH₂); 3.54 (t, 2H, OCH ₂CH₂N); 3.07 (ept, 1H,CHMe₂); 2.39 (t, 2H, OCH₂CH₂CH ₂N); 2.33 (t, 2H, OCH₂CH ₂N); 2.14(quint, 2H, OCH₂CH ₂CH₂N); 1.22 (d, 6H, CHMe ₁)

Analogously, the following product can be prepared:

-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-{3-[2-(4-morpholinyl)ethoxy]phenyl}acetamide

¹H-NMR (DMSO-d₆) δ ppm: 12.11 (bs, 1H, CONH); 7.20 (t, 1H, H5 Ph); 7.13(d, 1H, thiazole CH); 6.7–6.9 (m, 3H, H2, H4, H6 Ph); 4.04 (t, 2H, OCH₂CH₂N); 3.66 (s, 2H, COCH₂); 3.55 (m, 4H, OCH₂CH ₂N morpholine); 3.08(m, 1H, CHMe₂); 2.66 (t, 2H, OCH₂CH ₂N); 2.44 (m, 4H, OCH₂CH ₂Nmorpholine); 1.22 (d, 6H, CHMe ₂);

-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-{3-[3-(1-pirrolidinyl)propoxy]phenyl}acetamide

¹H-NMR (DMSO-d₆) δ ppm: 12.1 (bs, 1H, CONH); 7.19 (t, 1H, H5 Ph); 7.13(d, 1H, thiazole CH); 6.7–6.9 (m, 3H, H2, H4, H6 Ph); 3.97 (t, 2H, OCH₂CH₂CH₂N); 3.66 (s, 2H, COCH₂); 3.08 (m, 1H, CHMe₂); 2.50 (m, 2H,OCH₂CH₂CH ₂N); 2.41 (m, 4H, CH ₂N pirrolidine); 1.85 (m, 2H, OCH₂CH₂CH₂N); 1.65 (m, 4H, CH ₂CH₂N pirrolidine); 1.23 (d, 6H, CHMe ₂);

-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-{3-[3-(4-methyl-1-piperazinyl)propoxy]phenyl}acetamide

¹H-NMR (DMSO-d₆) δ ppm: 12.1 (bs, 1H, CONH); 7.19 (t, 1H, H5 Ph); 7.13(d, 1H, thiazole CH); 6.7–6.9 (m, 3H, H2, H4, H6 Ph); 3.95 (t, 2H, OCH₂CH₂CH₂N); 3.66 (s, 2H, COCH₂); 3.08 (m, 1H, CHMe₂); 2.15–2.45 (m, 10H,OCH₂CH₂CH ₂N+piperazine); 2.11 (s, 3H, NMe); 1.82 (m, 2H, OCH₂CH ₂CH₂N);1.22 (d, 6H, CHMe ₂).

-   2-{3-[2-(dimethylamino)ethoxy]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide

¹H-NMR (DMSO-d₆) δ ppm: 12.08 (bs, 1H, CONH); 7.2–6.90 (m, 5H,Ph+thiazole CH); 4.00 (t, 2H, OCH ₂CH₂N); 3.66 (s, 2H, COCH₂); 3.07 (m,1H, CHMe₂); 2.59 (t, 2H, OCH₂CH ₂N); 2.11 (s, 3H, NMe); 2.19 (s, 6H, Me² N); 1.22 (d, 6H, CHMe ₂);

-   2-{3-[3-(dimethylamino)propoxy]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide

¹H-NMR (DMSO-d₆) δ ppm: 12.05 (bs, 1H, CONH); 7.19–6.79 (m, 5H,Ph+thiazole CH); 3.95 (t, 2H, OCH ₂CH₂CH₂N); 3.66 (s, 2H, COCH₂); 3.08(m, 1H, CHMe₂); 2.32 (t, 2H, OCH₂CH₂CH ₂N); 2.11 (s, 3H, NMe ² ); 1.81(m, 2H, OCH₂CH ₂CH₂N); 1.22 (d, 6H, CHMe ₂)

EXAMPLE 25 Preparation of2-[N-[2′-N′-(ethoxycarbonyl-methyl)-amino]acetyl]-amino-5-bromo-thiazole

A solution of N-(5-bromo-1,3-thiazol-2-yl)-2-bromoacetamide (0.35 g,1.17 mmol) in DMF (5 ml) was added dropwise to a solution of glycineethyl ester hydrochloride (0.33 g, 2.33 mmol) and triethylamine (0.49ml, 3.5 mmol) in DMF (10 ml). After 3 hours at room temperature, thereaction mixture was heated at 40° C. for about 5 hours and then dilutedwith water and extracted with methylene chloride. The combined organiclayers were washed with brine, dried, concentrated and chromatographedon silica gel using cyclohexane:ethyl acetate 7:3 as eluent. The titlecompound was obtained as a colourless solid (0.15 g, 43%)

m.p. 115–116° C.

¹H-NMR (DMSO-d₆) δ ppm: 7.46 (s, 1H, H4thiaz), 4.05 (q, 2H, OCH2CH₃),3.49 (s, 2H, NHCOCH ₂), 3.4 (s, 2H, NHCH₂), 1.18 (t, 3H, OCH₂ CH ₃).

Analogously, the following compound can be prepared:

-   2-anilino-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide: m.p. 143–145°    C.

¹H-NMR (DMSO-d°) δ ppm: 11.92 (s, 1H, NHCO), 7.13 (s, 1H, H4thiaz),7.06–6.6 (m, 5H, Ph), 6.0 (t, 1H, NHCH₂), 3.95 (d, 2H, NHCH ₂), 3.08 (m,1H, CHMe₂), 1.23 (d, 6H, CHMe ₂)

EXAMPLE 26 Preparation ofN-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-bromophenyl)acetamide

To a suspension of resin N-Cyclohexylcarbodiimide N′-methylpolystyrene(0.251 g, 2.39 mmol g, 0.6 mmol), previously washed with DCM (3×5 ml),in DCM (4 ml) at room temperature, 2-bromophenylacetic acid (0.086 g,0.4 mmol) was added. After 10 min., a solution of2-amino-5-isopropyl-1,3-thiazole (0.0284 g, 0.2 mmol) in DCM (4 ml) wasadded. The mixture was shaked for 24 hours at room temperature, theresin filtered and washed with DCM (3×10 ml). The filtrated werecombined, washed with water, 5% HCl, water, saturated sodium bicarbonateand water, dried over sodium sulfate and evaporated.

¹H-NMR (DMSO-d₅) δ ppm:10.05 (s broad, 1H, NHCOCH₂), 7.6–7.2 (m, 4H,Ar), 7.08 (s, 1H, H4thiaz), 3.98 (s, 2H, NHCOCH ₂), 3.11 (m, 1H, CHMe₂),1.31 (d, 6H, CHMe ₂)

All the compounds were characterised by Mass Spectroscopy (MS). LC-MSconfirmed that in each case the principle component had a molecular ioncorresponding to the expected product.

Chromatography: Reverse phase HPLC with UV detection were run.

-   Mobile A: water (0.1% TFA)-   Mobile B: acetonitrile:water 95:5 (0.1% TFA)-   Flow rate: 1 ml/min-   Gradient: 10–100% B in 12 minutes, hold 100% B 3 min, return 10% B    in 5 min-   Detection: UV monitor 215, 254 and 300 nm-   Sample were prepared as dilute solutions in acetonitrile (1—1.5 mM).-   The compounds showed an HPLC area % ranging from 40 to 100%.

Starting from the suitable carboxylic acid, the following compounds canbe prepared:

-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,3,4,5,6-pentafluorophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-chlorophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-nitrophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-trifluoromethylphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-methoxyphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,5-dimethoxyphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,5-difluorophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4,5-trimethoxyphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,6-dichlorophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-chloro-6-fluorophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,5-dimethoxyphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,5-difluorophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,5-bis-trifluoromethylphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methylthiophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methoxyphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-bromophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-chlorophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-nitrophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2′-yl)-2-(4-trifluoromethylphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methylphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-trifluoromethylphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-chlorophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-methoxyphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,4-dinitrophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,4-dichlorophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,4-difluorophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-benzyloxy-3-methoxyphenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4-dichlorophenyl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4-difluorophenyl)acetamide;-   2-cyclopentyl-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide;-   2-cyclohexyl-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2,2-diphenylacetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-nitrophenoxy)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-nitrophenyl)propanamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-isobutylphenyl)propanamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-oxo-2-phenylacetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3-methyl-2-phenylpentanamide;-   (E, Z)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-2-butenamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)bicyclo[4.2.0]octa-1,3,5-triene-7-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl)butanamide;-   tert-butyl    (1R)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-phenylethylcarbamate;-   (1R)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-phenylethyl    acetate;-   (1S)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-phenylethyl    acetate;-   2-(acetylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide;-   (R)-2-(methoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide;-   3,3,3-trifluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxy-2-phenylpropanamide;-   2-(2,4-dinitrophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl) acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(5-benzyloxy-1H-indol-3-yl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-methoxy-2-methyl-1H-indol-3-yl)acetamide;-   2-(1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-oxoacetamide;-   2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;-   4-(1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)butanamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3-(2-thienyl)propanamide    2-(5-chloro-1-benzothiophen-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;-   2-(1-benzothiophen-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;-   2-[2-(formylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)-2-(methoxyimino)acetamide;-   2-{2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)-2-(methoxyimino)acetamide;-   2-chloro-N-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)acetamide;-   Ethyl    2-({[2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-(1H-pyrazol-3-yl)ethylidene]amino}oxy)acetate;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-oxo-4-(4-methylphenyl)butanamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-(4-nitrophenyl)butanamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-phenylbutanamide;-   benzyl 4-[(5-isopropyl-1,3-thiazol-2-yl)amino]-4-oxobutylcarbamate;-   4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)butanamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-(4-methoxy-1-naphthyl)-4-oxobutanamide;-   3-(2-chlorophenoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;-   3-(4-methylphenoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;-   3-cyclopentyl-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;-   3-cyclohexyl-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-methylpentanamide;-   3-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;-   3-(4-methoxyphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;-   3-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;-   3-phenyl-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-5-oxo-5-phenylpentanamide;-   2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-phenylethyl acetate;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)phenyl]propanamide;-   1-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)cyclopentanecarboxamide;-   1-phenyl-N-(5-isopropyl-1,3-thiazol-2-yl)cyclopentanecarboxamide;-   2-(3-bromo-4-methoxyphenyl)-N-(5-isopropyl    1,3-thiazol-2-yl)acetamide;-   2-(2-nitro-4-trifluoromethylphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;-   5-cyclohexyl    1-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylbenzyl)    (2S)-2-[(tert-butoxycarbonyl)amino]pentanedioate;-   2-(5,6-dimethyl-1H-benzimidazol-1-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;-   2-[5-(4-chlorophenyl)-2H-1,2,3,4-tetraazol-2-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-[5-(1-pyrrolidinyl)-2H-1,2,3,4-tetraazol-2-yl]acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-methyl-1-benzothiophen-2-yl)acetamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4,4-bis(4-methylphenyl)-3-butenamide;-   2-cyclopropyl-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;-   N-{4-bromo-6-[(5-isopropyl-1,3-thiazol-2-yl)amino]-6-oxohexyl}benzamide;-   2-cyclopentyl-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;-   benzyl 6-[(5-isopropyl-1,3-thiazol-2-yl)amino]-6-oxohexylcarbamate;-   N˜1˜-(5-isopropyl-1,3-thiazol-2-yl)-N˜4˜-(2-propynyl)-2-butenediamide-   4-(2,4-dimethylphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-4-oxobutanamide;-   4-(4-benzyloxyphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-4-oxobutanamide;-   4-(thiphen-2-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)-4-oxobutanamide;-   benzyl    2-{[(benzyloxy)carbonyl]amino}-5-[(5-isopropyl-1,3-thiazol-2-yl)amino]-5-oxopentanoate;-   4-(1H-indol-3-yl)-N-{3-[(5-isopropyl-1,3-thiazol-2-yl)amino]-3-oxopropyl}butanamide;-   4-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}phenyl    4-chlorobenzenesulfonate;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-{[(2-methoxyanilino)carbonyl]amino}benzamide;-   4-{[2-(isopropylsulfonyl)acetyl]amino}-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-{[2-(phenylsulfanyl)acetyl]amino}benzamide;-   4-[(diethylamino)sulfonyl]-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   2-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   3,5-difluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   3-{[(2-fluoroanilino)carbonyl]amino}-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-1-phenyl-5-propyl-1H-pyrazole-4-carboxamide;-   3-chloro-4-(isopropylsulfonyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-(methylsulfanyl)-2-thiophenecarboxamide;-   3-iodo-4-(isopropylsulfonyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-5-(methylsulfanyl)-2-thiophenecarboxamide;-   2-{[(4-chlorophenyl)sulfonyl]methyl}-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methyl-1,3-thiazole-5-carboxamide;-   5-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-(trifluoromethyl)-3-furamide;-   3,5-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   3,4-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   2,4-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   2,3-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   3-iodio-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   2-iodio-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   4-iodio-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   3-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   4-chloro-2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   5-bromo-2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   3-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   2,4-difluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   3,4-difluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   2,3,4,5,6-pentafluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-methyl-3-nitrobenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-nitrobenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3-methyl-2-nitrobenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethyl-4-nitrobenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxy-2-nitrobenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-2-nitrobenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxy-3-nitrobenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-4-nitrobenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dinitrobenzamide;-   5-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-nitrophenyl    octanoate;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-nitrobenzamide;-   4-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-nitrobenzamide;-   4-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide;-   2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-nitrobenzamide;-   5-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide;-   2-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)-5-nitrobenzamide;-   4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-nitrobenzamide;-   4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitro-4-(trifluoromethyl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-bis(trifluoromethyl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2,6-bis(trifluoromethyl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-(trifluoromethyl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide;-   3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-(trifluoromethyl)benzamide;-   2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide;-   5-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide;-   2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-(trifluoromethyl)benzamide;-   4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide;-   methyl 2-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}benzoate;-   4-cyano-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   3-cyano-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3-methylbenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-methylbenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-methylbenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-vinylbenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-(2-phenylethynyl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-4-methylbenzamide;-   2-benzyl-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenethylbenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylbenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-phenylbenzamide;-   4-(tert-butyl)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-isopropylbenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-pentylbenzamide;-   3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methylbenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3,4-dimethylbenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethylbenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-(methylsulfonyl)benzamide;-   3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxybenzamide;-   3-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxybenzamide;-   5-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxybenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxybenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxybenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxybenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3,4-dimethoxybenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethoxybenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2,4-dimethoxybenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2,3-dimethoxybenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3-phenoxybenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenoxybenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-phenoxybenzamide;-   2-ethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   4-ethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3,4,5-trimethoxybenzamide;-   3,4-diethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   3,4,5-triethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide-   N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-4-(methoxymethoxy)benzamide;-   4-butoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-propoxybenzamide;-   4-isopropoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-1,3-benzodioxole-5-carboxamide;-   4-(benzyloxy)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   4-(2-cyclohexen-1-yloxy)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-(trifluoromethoxy) benzamide;-   4-(difluoromethoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-(methylsulfanyl)benzamide;-   2-[(4-chlorophenyl)sulfinyl]-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-[(4-nitrophenyl)sulfinyl]benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-[(4-methylphenyl)sulfonyl]-3-nitrobenzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3[(trifluoromethyl)sulfanyl]benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxy-4-(methylsulfanyl)benzamide;-   2-[(2-cyanophenyl)sulfanyl]-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N˜1˜,N˜1˜-diethyl-3,6-difluoro-N˜2˜-(5-isopropyl-1,3-thiazol-2-yl)phthalamide;-   4-formyl-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   2-formyl-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   4-{[(2,5-dimethoxyanilino)carbonyl]amino}-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   4-(hydroxymethyl)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   4-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-nitrobenzyl    acetate;-   4-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-nitrobenzyl    4-(acetylamino)-3-iodobenzoate;-   4-(acetylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-[(2-phenylacetyl)amino]benzamide;-   4-(acetylamino)-3-iodo-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   4-amino-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   4-(dimethylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   3-(dimethylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   2-(methylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-[3-(trifluoromethyl)anilino]benzamide;-   3-{[(5-bromo-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]amino}-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-4-(1H-pyrrol-1-yl)benzamide;-   2,6-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)isonicotinamide;-   2-(4-bromophenyl)-6-(4-iodophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)isonicotinamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-[3-(trifluoromethyl)anilino]nicotinamide;-   5,6-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)nicotinamide;-   2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-6-methylnicotinamide;-   2,6-dichloro-5-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)nicotinamide-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenoxynicotinamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-6-(2,2,2-trifluoroethoxy)nicotinamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2,6-dimethoxynicotinamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-quinoxalinecarboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-pyrazinecarboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-8-quinolinecarboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-4-quinolinecarboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-1H-pyrazole-3-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-1H-pyrazole-4-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-phenyl-2H-1,2,3-triazole-4-carboxamide;-   2-[(2,1,3-benzoxadiazol-5-yloxy)methyl]-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methyl-1,3-thiazole-5-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-9H-fluorene-1-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-7-methoxy-1-benzofuran-2-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-1-[(4-methylphenyl)sulfonyl]-1H-pyrrole-3-carboxamide;-   2-ethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)-1-naphthamide;-   4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-1-naphthamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-naphthamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-9,10-dioxo-9,10-dihydro-2-anthracenecarboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-9-oxo-9H-fluorene-4-carboxamide-   N-(5-isopropyl-1,3-thiazol-2-yl)-9-oxo-9H-fluorene-1-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-8-oxo-5,6,7,8-tetrahydro-2-naphthalenecarboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-1,3-dioxo-1,3-dihydro-2-benzofuran-5-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-5-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-4-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-1-methyl-2-phenyl-1H-indole-5-carboxamide;-   2-butyl-N-(5-isopropyl-1,3-thiazol-2-yl)-1-methyl-1H-indole-5-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-6-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-5-methoxy-1H-indole-2-carboxamide;-   1-allyl-2-butyl-N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-5-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-1-methyl-1H-indole-2-carboxamide;-   1-benzyl-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-1H-indole-5-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-1H-1,2,3-benzotriazole-5-carboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethyl-4-isoxazolecarboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3-thiophenecarboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3-methyl-2-thiophenecarboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-thiophenecarboxamide;-   5-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)-2-thiophenecarboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-3-[(2,3,3-trichloroacryloyl)amino]-2-thiophenecarboxamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-5-(4-nitrophenyl)-2-furamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-5-(2-nitrophenyl)-2-furamide;-   5-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-5-[3-(trifluoromethyl)phenyl]-2-furamide;-   5-(4-chloro-2-nitrophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide;-   N-(5-isopropyl-1,3-thiazol-2-yl)-5-(4-methyl-2-nitrophenyl)-2-furamide-   5-[2-chloro-5-(trifluoromethyl)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide;-   tert-butyl    (1S)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-1-methyl-2-oxoethylcarbamate-   tert-butyl    (1S,2S)-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-methylbutylcarbamate-   tert-butyl    2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate-   tert-butyl    (1S)-5-amino-1-([(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}pentylcarbamate-   tert-butyl    4-[(imino{[(4-methylphenyl)sulfonyl]amino}methyl)amino]-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}butylcarbamate-   tert-butyl    1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-3-(tritylamino)propylcarbamate-   tert-butyl    (1S)-1-(benzyloxymethyl)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate-   tert-butyl    (1S)-1-benzyl-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate-   tert-butyl    (1R)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-(benzylthiomethyl)ethylcarbamate-   benzyl    (3S)-3-[(tert-butoxycarbonyl)amino]-4-[(5-isopropyl-1,3-thiazol-2-yl)amino]-4-oxobutanoate-   tert-butyl    (2S)-2-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-1-pyrrolidinecarboxylate-   tert-butyl    (1S)-1-(1H-indol-3-ylmethyl)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate-   tert-butyl    (1S)-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-3-(methylsulfanyl)propylcarbamate-   tert-butyl    (1S)-2-benzyloxy-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}propylcarbamate-   tert-butyl    (1S)-1-(4-benzyloxybenzyl)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate-   tert-butyl    (1S)-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-methylpropylcarbamate-   tert-butyl    (1S)-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-3-methylbutylcarbamate    and-   benzyl    (4S)-4-[(tert-butoxycarbonyl)amino]-5-[(5-isopropyl-1,3-thiazol-2-yl)amino]-5-oxopentanoate.

Following the same procedure as reported in Example 3, the compoundsdescribed in the table (I) below can be prepared:

TABLE I mp MOLSTRUCTURE ° C. ¹H-NMR Solvent

12.23(s broad, 1H, NHCOCH₂),8.22–7.62(m, 4H, Ar), 7.15(s, 1H, H4thiaz),3.91(s, 2H,NHCOCH ₂), 3.08(m, 1H, CHMe₂),1.22(d, 6H, CHMe ₂) DMSO-d⁶

9.81(s broad, 1H, NHCOCH₂),7.5–7.3(m, 4H, Ar), 7.11(s, 1H,H4thiaz),4.83(s, 1H, NHCOCH),3.44(s, 3H, Ome) 3.11(m, 1H,CHMe₂), 1.3(d, 6H, CHMe₂) DMSO-d⁶

124–125 12.06(s broad, 1H, NHCO), 7.13(s, 1H, H4thiaz) 6.92–6.81(m,3H,Ar), 3.72(s, 3H, OMe), 3.70(s,3H, OMe), 3.61(s, 2H, NHCOCH ₂),3.07(m,1H, CHMe₂), 1.22(d, 6H,CHMe ₂) DMSO-d⁶

77–78 12.05(s broad, 1H, NHCO),7.38–7.29(m, 5H, Ar), 7.12(s,1H,H4thiaz), 4.95(s, 1H, CHOMe),3.23(s, 2H, CHOMe), 3.05(m, 1H,CHMe₂),1.20(d, 6H, CHMe ₂) DMSO-d⁶

136–137 12.08(s broad, 1H, NHCOCH₂), 7.28(d, 2H, Ar), 7.13(s,1H,H4thiaz), 7.1(d, 2H, Ar), 3.65(s, 2H, NHCOCH ₂), 3.06(m, 1H,CHMe₂),2.98(s, 6H, NMe ₂), 1.22(d, 6H, CHMe ₂) DMSO-d⁶

130–131 12.22(s, 1H, NHCO), 7.85–7.48(m, 7H, Ar), 7.14(s, 1H,H4thiaz),3.89(s, 2H, CH ₂CO),3.07(m, 1H, CHMe₂), 1.22(d, 6H,CHMe ₂) DMSO-d⁶

130–131 12.16(s, 1H, NHCO), 7.52–7.29(m, 4H, Ar), 7.14(s, 1H,H4thiaz),3.73(s, 2H, CH ₂CO),3.08(m, 1H, CHMe₂), 1.22(d, 6H,CHMe ₂) DMSO-d⁶

177–178 8.07–7.48(m, 7H, Ar), 7.15(s, 1H, H4thiaz), 4.22(s, 2H,CH ₂CO),3.06(m, 1H, CHMe₂),1.20(d, 6H, CHMe ₂) DMSO-d⁶

223–224 12.61(s, 1H, NHCO), 7.69–7.51(m, 4H, Ar), 7.19(s, 1H,H4thiaz),4.55(dd, 1H, CHCO),3.08(m, 1H, CHMe₂), 2.89(m, 2H,COCH ₂CH), 1.22(d, 6H,CHMe ₂) DMSO-d⁶

105–106 12.50(s, 1H, NHCO), 7.53–7.51(m, 5H, Ar), 7.18(s, 1H,H4thiaz),6.12(d, 1H, J_(H−F)=46.8,CHF), 3.09(m, 1H, CHMe₂), 1.22(d, 6H, CHMe ₂)DMSO-d⁶

150–152 11.20(s broad, 1H, NHCO),7.28–7.07(m, 5H, Ar+H4thiaz), 3.80(s,2H, CH ₂CO), 3.13(m, 1H,CHMe₂), 1.32(d, 6H, CHMe ₂) DMSO-d⁶

164–166 11.45(s broad, 1H, NHCO),7.37–7.14(m, 5H, Ar+H4thiaz), 3.88(s,2H, NHCOCH ₂), 3.12(m, 1H,CHMe₂), 1.32(d, 6H, CHMe ₂) DMSO-d⁶

 98–100 8.35(s broad, 1H, NHCO), 7.40(m, 5H, Ar), 6.99(s, 1H,H4thiaz),3.10(m, 1H, CHMe₂),1.78(m, 2H, CH₂), 1.29(m, 2H,CH₂), 1.25(d, 6H, CHMe₂) CDCl₃

130–132 12.06(s broad), 1H, NHCOCH₂), 7.13(s, 1H, H4thiaz),6.86–6.75(m,3H, Ar), 5.96(s, 2H, OCH ₂O),3.60(s, 2H, NNCOCH ₂),3.05(m,1H, CHMe₂), 1.22(d, 6H, CHMe ₂) DMSO-d⁶

100–102 12.1(s broad, 1H, NHCOCH₂),7.2–7(m, 4H, Ar+H4thiaz), 3.64(s,2H,NHCOCH ₂), 3.07(m, 1H, CHMe₂),2.8–1.97(m, 6H, —CH₂CH₂CH₂—),1.22(d, 6H,CHMe ₂) DMSO-d⁶

 98–100 12.06(s broad, 1H, NHCO), 7.3(m, 5H, Ar), 7.03(s, 1H,H4thiaz),3.79(q, 1H, CHMe), 3.10(m, 1H, CHMe₂), 1.59(d, 3H,CHMe), 1.30(d, 6H,CHMe ₂) DMSO-d⁶

167–169 10(s broad, 1H, NHCOCH₂), 7.6–7.4(m, 9H, Ar), 7.04(s,1H,H4thiaz), 3.84(s, 2H, NHCOCH ₂),3.11(m, 1H, CHMe₂), 1.31(d, 6H,CHMe₂) DMSO-d⁶

115–116 12.06(s broad, 1H, NHCO), 7.26(m, 5H, Ar), 6.99(s, 1H,H4thiaz),3.79(q, 1H, CHMe), 3.10(m, 1H, CHMe₂), 1.59(d, 3H,CHMe), 1.30(d, 6H,CHMe ₂) DMSO-d⁶

112–114 12.06(s broad, 1H, NHCO), 7.33(m, 5H, Ar), 7.11(s, 1H,H4thiaz),3.93(q, 1H, CHMe), 3.07(m, 1H, CHMe₂), 1.40(d, 3H,CHMe), 1.22(d, 6H,CHMe ₂) DMSO-d⁶

124–126 12.01(s broad, 1H, NHCO),7.11–6–65(m, 5H, Ar+H4thiaz), 3.55(s,2H, NHCOCH ₂), 2.83(s, 6H,NMe ₂), 2.56(d, 2H, CH ₂iPr), 1.74(m, 1H,CHMe₂), 0.87(d, 6H,CHMe ₂) DMSO-d⁶

139–141 9.90(s broad, 1H, NHCO), 7.04(s, 1H, H4thiaz), 6.78(m, 3H,Ar),5.96(s, 2H, OCH ₂O), 3.72(s,2H, NHCOCH ₂), 2.60(d, 2H,CH ₂iPr), 1.85(m,1H, CHMe₂), 0.93(d, 6H, CHMe₂) CDCl₃

175–177 12.0(s broad, 1H, NHCO), 7.28(m, 6H, CH₂ Ph+H4thiaz),7.08–6.64(m, 4H, Ar), 4.04(s, 2H, CH ₂Ph),3.53(s, 2H, NHCOCH ₂),2.82(s,6H, NMe ₂) DMSO-d⁶

88–90 12.08(s broad, 1H, NHCO),7.20–6.81(m, 5H, Ar+H4thiaz), 4.01(dd,2H, OCH ₂CH₂OMe), 3.68(s, 2H,NHCOCH ₂), 3.61(dd, 2HOCH₂ CH ₂OMe), 3.3(s,3H,OCH₂CH₂OMe), 3.05(m, 1H, CHMe₂),1.22(s, 6H, CHMe ₂) DMSO-d⁶

230–231 12.81(s broad, 1H, NHCO),8.63–7.79(m, 3H, Ar), 7.71(s, 2H,NH₂),7.24(s, 1H, H4thiaz), 3.12(m, 1H, CHMe₂), 1.27(d, 6H,CHMe ₂) DMSO-d⁶

181–182 12.47(s broad, 1H, NHCO),8.13–7.37(m, 4H, Ar), 7.23(s,1H,H4thiaz), 3.13(m, 1H, CHMe₂),1.27(d, 6H, CHMe ₂) DMSO-d⁶

12.0(s broad, 1H, NHCO),8.89–7.82(m, 4H, Ar), 7.27(s, 1H,H4thiaz),3.13(m, 1H, CHMe₂),1.28(d, 6H, CHMe ₂) DMSO-d⁶

263–264 12.74(s broad, 1H, NHCO),8.11–8.0(2s, 2H, Ar), 7.82(s, 2H,NH₂),7.24(s, 1H, H4thiaz), 3.15(m, 1H, CHMe₂), 1.27(d, 6H,CHMe ₂) DMSO-d⁶

204–206 12.6(s broad, 1H, NHCO),8.06–7.60(m, 3H, Ar), 7.23(s,1H,H4thiaz), 3.12(m, 1H, CHMe₂),1.27(d, 6H, CHMe ₂) DMSO-d⁶

148–150 8.54–8.31(m, 3H, Ar), 6.98(s, 1H, H4thiaz), 3.43(s, 3H,SO₂ Me)3.14(m, 1H, CHMe₂), 1.35(d, 6H, CHMe ₂) CDCl₃

173–175 8.16–8.06(2d, 4H, Ar), 7.25(s, 1H, H4thiaz), 3.88(s, 3H,COOMe),3.14(m, 1H, CHMe₂), 1.28(d, 6H, CHMe ₂) DMSO-d⁶

164–166 8.50–7.86(m, 3H, Ar), 7.24(s, 1H, H4thiaz), 3.15(m, 1H,CHMe₂),1.28(d, 6H, CHMe ₂) DMSO-d⁶

178–179 12.4(s broad, 1H, NHCO),8.12–7.21(m, 3H, Ar), 7.22(s,1H,H4thiaz), 3.2–2.48(m, 5H, CHMe₂+piperazine), 2.22(s, 3H, NMe),1.27(d,6H, CHMe ₂) DMSO-d⁶

12.6(s broad, 1H, NHCO),7.73–7.57(m, 3H, Ar), 7.22(s, 1H,H4thiaz),3.15(m, 1H, CHMe₂),1.27(d, 6H, CHMe ₂) DMSO-d⁶

12.6(s broad, 1H, NHCO),8.16–8.05(m, 4H, Ar), 7.24(s, 1H,H4thiaz),3.13(m, 1H, CHMe₂),2.62(s, 3H, COMe), 1.28(d, 6H,CHMe ₂) DMSO-d⁶

207–209 9.4(s broad, 1H, NHCO), 8.3(s,1H, NH), 7.55–6.98(m,6H,indole+H4thiaz), 3.96(s, 2H,COCH₂), 3.10(m, 1H, CHMe₂), 1.30(d, 6H,CHMe ₂) CDCl₃

116–118 9.80(s broad, 1H, NHCO),7.37–7.05(m, 3H, Ar), 7.04(d,1H,H4thiaz), 3.84(s, 2H, COCH₂), 3.11(m, 1H, CHMe₂), 1.32(d, 6H,CHMe ₂)CDCl₃

148–150 10.20(s broad, 1H, NHCO),7.28–7.01(m, 4H, Ar+H4thiaz), 4.02(s,2H, COCH₂), 3.13(m, 1H,CHMe₂), 1.32(d, 6H, CHMe ₂) CDCl₃

170–172 12.05(s broad, 1H, NHCO), 10.82(s, 1H, NH), 7.48–6.90(m,5H,indole+H4thiaz), 3.74(s, 2H,COCH₂), 3.06(m, 1H, CHMe₂), 2.36(s, 3H,Me), 1.21(d, 6H, CHMe ₂) DMSO-d⁶

163–165 12.07(s broad, 1H, NHCO),7.57–7.01(m, 6H,indole+H4thiaz),3.79(s, 2H, COCH₂), 3.74(s, 3H,NMe), 3.05(m, 1H, CHMe₂),1.21(d, 6H, CHMe ₂) DMSO-d⁶

155–157 10.20(s broad, 1H, NHCO),7.88–7.40(m, 5H, Ar), 6.95(s,1H,H4thiaz), 4.04(s, 2H, COCH₂), 3.07(m, 1H, CHMe₂), 1.27(d, 6H,CHMe ₂)DMSO-d⁶

234–236 11.3(s broad, 1H, NHCO),7.52–6.28(m, 5H, Ar+H4thiaz), 3.93(s,2H, COCH₂), 3.87(s, 3H, OMe),3.10(m, 1H, CHMe₂), 1.27(d, 6H,CHMe ₂)DMSO-d⁶

161–163 12.19(s, 1H, NHCO), 8.49–7.34(m, 4H, Ar), 7.12(s, 1H,H4thiaz),2.56(d, 2H, CH ₂iPr),1.75(m, 1H, CHMe₂), 0.86(d, 6H,CHMe ₂) DMSO-d⁶

166–168 12.20(s, 1H, NHCO), 8.48–7.24(m, 10H, 2Xar+H4thiaz), 4.06(s,2H,CH ₂Ph), 3.77(s, 2H, CH ₂CO) DMSO-d⁶

164–167 8.63–7.9(m, 5H, Ar), 7.11(s,1H, H4thiaz), 3.85(s, 2H,COCH₂),3.15(m, 1H, CHMe₂), 1.29(d, 6H,CHMe ₂) CDCl3

11.6(s broad, 1H, NHCO), 7.10(s, 1H, H4thiaz), 3.67(s, 3H,CH ₃OCO),3.15(m, 1H, CHMe₂),2.60(m, 2H, CH ₂CH₂CH₂), 2.46(m,2H, CH₂CH₂ CH ₂),2.09(m, 2H,CH₂ CH ₂CH₂), 1.34(d, 6H, CHMe ₂) CDCl₃

114–117 10.6(s broad, 1H, NHCO), 7.36(m, 5H, Ar), 7.10(s, 1H,H4thiaz),6.61(d, 1H, J=15.8,CH═CHPh), 6.36(dt, 1H, J=15.8,7.3, CH═CHPh), 3.43(dd,2H,J=7.3, 1.3, COCH₂), 3.14(m, 1H,CHMe₂), 1.33(d, 6H, CHMe ₂) CDCl₃

217–220 12.09(s broad, 1H, NHCO), 11.5(s, 1H, NH), 7.78–7.16(m,4H,indole), 7.13(s, 1H, H4thiaz),3.78(s, 2H, COCH₂), 3.07(m,1H, CHMe₂),1.21(d, 6H, CHMe ₂) DMSO-d⁶

222–225dec. 12.07(s, 1H, NHCO), 11.03(s,1H, NH), 7.3–6.80(m, 5H,indole+H4thiaz), 3.77(s, 2H, COCH₂),3.06(m, 1H, CHMe₂), 1.22(d, 6H,CHMe₂) DMSO-d⁶

172–173 12.25(s, 1H, NHCO), 8.02–7.4(m,4H, Ar), 7.15(s, 1H,H4thiaz),4.0(s, 2H, COCH₂), 3.07(m, 1H,CHMe₂), 1.22(d, 6H, CHMe ₂)DMSO-d⁶

203–204 12.05(s, 1H, NHCO), 10.77(s,1H, NH), 7.22–6.70(m,5H,indole+H4thiaz), 3.75(s, 2H,COCH₂), 3.72(s, 3H, OMe), 3.07(m, 1H,CHMe₂), 1.22(d, 6H,CHMe ₂) DMSO-d⁶

163–164 12.89(s, 1H, NHCO), 10.75(s,1H, NH), 7.12–6.97(m,5H,indole+H4thiaz), 3.10(m, 1H,CHMe₂), 3.01(t, 2H, CH ₂CH₂CO),2.78(t,2H, CH₂ CH ₂CO), 1.25(d,6H, CHMe ₂) DMSO-d⁶

186–187 12.7(s broad, 1H, NHCO), 8.18(d, 1H, J=7.8, Ar), 7.71(d,1H,J=7.8, Ar), 7.24(s, 1H, H4thiaz),3.15(m, 1H, CHMe₂), 1.27(d, 6H,CHMe₂) DMSO-d⁶

10.8(s broad, 1H, NHCO), 7.45(s, 1H, H4thiaz), 3.33(m, 1H,CHMe₂),2.54(m, 2H, CH ₂CHMe₂),2.42(m, 1H, CH₂ CHMe₂), 1.53(d,6H, CH₂CHMe ₂),1.21(d, 6H, CHMe ₂) CDCl₃

12.4(s broad, 1H, NHCO),8.05–7.51(m, 5H, Ph), 7.23(s, 1H,H4thiaz),3.13(m, 1H, CHMe₂),1.28(d, 6H, CHMe ₂) DMSO-d⁶

11.8(s broad, 1H, NHCO), 7.11(s, 1H, H4thiaz), 3.08(m, 1H,CHMe₂),2.25(d, 2H, CH ₂CO), 2.42(m, 1H, CH₂ CHMe₂), 1.23(d, 6H,CHMe ₂),1.8–0.8(m, 11H,cyclohexyl) DMSO-d⁶

8.13(d, 1H, H3fur), 7.84(d, 1H,H5fur), 7.25(d, 1H, H4thiaz),6.69(dd, 1H,H4fur), 7.45(s,1H, H4thiaz), 3.20(m, 1H, CHMe₂),1.39(d, 6H, CHMe ₂)CDCl₃

12.7(s broad, 1H, NHCO),7.54–6.82(m, 3H, H4thiaz+furane),3.10(m, 1H,CHMe₂), 1.26(d, 6H,CHMe ₂), DMSO-d⁶

1. A compound which is a 2-amino-1,3-thiazole derivative of formula (I)

wherein R is isopropyl; R₁ is an optionally further substituted groupselected from: i) straight or branched C₁–C₈ alkyl or C₂–C₆ alkenyl; ii)3 to 6 membered carbocycle or 5 to 7 membered heterocycle ring; iii)aryl or arylcarbonyl; iv) arylalkyl with from 1 to 8 carbon atoms withinthe straight or branched alkyl chain; v) arylalkenyl with from 2 to 6carbon atoms within the straight or branched alkenyl chain; vi) anoptionally protected amino acid residue; or a pharmaceuticallyacceptable salt thereof.
 2. A compound of formula (I), according toclaim 1, wherein R₁ is an optionally substituted group selected fromstraight or branched C₁–C₄ alkyl or alkenyl, aryl or arylalkyl with from1 to 4 carbon atoms within the alkyl chain or it is an optionallyprotected amino acid residue.
 3. A process for producing a compound offormula (I), as defined in claim 1, which process comprises reacting acompound of formula (II)

with a compound of formula (III)R₁—COX  (III) wherein R and R₁ are as defined in claim 1 and X ishydroxy or a suitable leaving group; and, if desired, converting a2-amino-1,3-thiazole derivative of formula (I) into another suchderivative of formula (I), and/or into a salt thereof.
 4. A processaccording to claim 3 wherein X is hydroxy, bromine or chlorine.
 5. Apharmaceutical composition comprising one or more pharmaceuticallyacceptable carriers and/or diluents and, as the active principle, aneffective amount of a compound of formula (I) as defined in claim
 1. 6.A compound of formula (I) according to claim 1, whenever appropriate inthe form of a pharmaceutically acceptable salt, selected from the groupconsisting of:N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-hydroxyphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-methoxyphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-chlorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-hydroxyphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4-dihydroxyphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-hydroxy-3-methoxyphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methoxyphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-chlorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-acetamide;N-(5-isopropyl-thiazol-2-yl)-4-sulfamoyl-benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-butanamide;2-[3-(3-chloropropoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;2-[3-(2-chloroethoxy)phenyl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;2-(4-aminophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;4-amino-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;2-(2-amino-1,3-thiazol-4-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-{3-[3-(4-morpholinyl)propoxy]phenyl}acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-{3-[3-(4-morpholinyl)ethoxy]phenyl}acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-[3-(1-pirrolidinyl)propoxy]phenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-{3-[3-(4-methyl-1-piperazinyl)propoxy]phenyl}acetamide;2-{3-[2-(dimethylamino)ethoxy]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;2-{3-[3-(dimethylamino)propoxy]phenyl}-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;N-(5-isopropyl-1,3-thiazol-2.-yl)-2-[3-(2-methoxyethoxy)phenyl]acetamide;3-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-(4-methyl-piperazinyl)bezamide;2-anilino-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;(R)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylpropanamide;(S)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylpropanamide;N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;2,5-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;3,5-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;3,4-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;2,4-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;2,3-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;3-iodio-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;2-iodio-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;4-iodio-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;3-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;4-chloro-2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;5-bromo-2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;3-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;4-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;2,4-difluoro-N-(5-isopropyl-1,3-triazol-2-yl)benzamide;3,4-difluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;2,3,4,5,6-pentafluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-methyl-3-nitrobenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-nitrobenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-methyl-2-nitrobenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethyl-4-nitrobenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxy-2-nitrobenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-2-nitrobenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxy-3-nitrobenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-4-nitrobenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dinitrobenzamide;5-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-nitrophenyloctanoate; N-(5-isopropyl-1,3-thiazol-2-yl)-3-nitrobenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-nitrobenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-(methylsulfonyl)-3-nitrobepzamide;4-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-nitrobenzamide;6-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-nitrobenzamide;4-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide;2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-nitrobenzamide;5-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide;2-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)-5-nitrobenzamide;4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-nitrobenzamide;4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitrobenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-nitro-4-(trifluoromethyl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-bis(trifluoromethyl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2,6-bis(trifluoromethyl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(trifluoromethyl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide;3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-(trifluoromethyl)benzamide;2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide;5-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide;2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-(trifluoromethyl)benzamide;4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-3-(trifluoromethyl)benzamide;methyl 4-([(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}benzoate; methyl2-([(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl)benzoate;4-cyano-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;3-cyano-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-methylbenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-methylbenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-methylbenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-vinylbenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-(2-phenylethynyl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-4-methylbenzamide;2-benzyl-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenethylbenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylbenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-phenylbenzamide;4-(tert-butyl)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-isopropylbenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-pentylbenzamide;3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methylbenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3,4-dimethylbenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethylbenzamide;4-acetyl-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-(methylsulfonyl)benzamide;5-(aminosulfonyl)-2,4-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;5-(aminosulfonyl)-4-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;3-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxybenzamide;3-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxybenzamide;5-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxybenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-methoxybenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxybenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxybenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3,4-dimethoxybenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethoxybenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2,4-dimethoxybenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2,3-dimethoxybenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-phenoxybenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenoxybenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-phenoxybenzamide;2-ethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;4-ethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3,4,5-trimethoxybenzamide;3,4-diethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;3,4,5-triethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-methoxy-4-(methoxymethoxy)benzamide;4-butoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-propoxybenzamide;4-isopropoxy-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-1,3-benzodioxole-5-carboxamide;4-(benzyloxy)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;4-(2-cyclohexen-1-yloxy)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4(trifluoromethoxy)benzamide;4-(difluoromethoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4(methylsulfanyl)benzamide;2-[(4-chlorophenyl)sulfinyl)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-[(4-nitrophenyl)sulfinyl]benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-[(4-methylphenyl)sulfonyl]-3-nitrobenzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3 [(trifluoromethyl)sulfanyl]benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxy-4-(methylsulfanyl)benzamide;2-[(2-cyanophenyl)sulfanyl]-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-1,N-1-diethyl-3,6-difluoro-N-2-(5-isopropyl-1,3-thiazol-2-yl)phthalamide;4-formyl-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;2-formyl-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;4-{[(2,5-dimethoxyanilino)carbonyl]amino}-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;4-(hydroxymethyl)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;4-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-nitrobenzyl acetate;4-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-nitrobenzyl4-(acetylamino)-3-iodobenzoate;4-(acetylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-[(2-phenylacetyl)amino]benzamide;4-(acetylamino)-3-iodo-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;4-amino-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;4-(dimethylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;3-(dimethylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;2-(methylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-[3-(trifluoromethyl)anilino]benzamide;3-{[(5-bromo-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]amino}-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-(1H-pyrrol-1-yl)benzamide;2,6-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)isonicotinamide;2-(4-bromophenyl)-6-(4-iodophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)isonicotinamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-[3-(trifluoromethyl)anilino)nicotinamide;2,6-dichloro-N-(5-isopropyl. 1,3-thiazol-2-yl)nicotinamide;5,6-dichloro-N-(5-isopropyl-1,3-thiazol-2-yl)nicotinamide;2-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)-6-methylnicotinamide;2,6-dichloro-5-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)nicotinamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenoxynicotinamide;N-(5-isopropyl-1,3-thiazol-2-yl)-6-(2,2,2-trifluoroethoxy)nicotinamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2,6-dimethoxynicotinamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-quinoxalinecarboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-pyrazinecarboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-8-quinolinecarboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-4-quinolinecarboxamjde;N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-1H-pyrazole-3-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-1H-pyrazole-4-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-phenyl-2H-1,2,3-triazole-4-carboxamide;2-[(2,1,3-benzoxadiazol-5-yloxy)methyl]-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methyl-1,3-thiazole-5-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-9H-fluorene-1-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-7-methoxy-1-benzofrran2-carboxide;N-(5-isopropyl-1,3-thiazol-2-yl)-1-[(4-methylphenyl)sulfonyl]-1H-pyrrole-3-carboxamide;2-ethoxy-N-(5-isopropyl-1,3-thiazol-2-yl)-1-naphthamide;4-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-1-naphthamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-naphthamide;N-(5-isopropyl-1,3-thiazol-2-yl)-9,10-dioxo-9,10-dihydro-2-anthracenecarboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-9-oxo-9H-fluorene-4-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-9-oxo-9H-fluorene-1-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-8-oxo-5,6,7,8-tetrahydro-2-naphthalenecarboxarmde;N-(5-isopropyl-1,3-thiazol-2-yl)-1,3-dioxo-1,3-dihydro-2-benzofuran-5-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-5-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-4-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-1-methyl-2-phenyl-1H-indole-5-carboxamide;2-butyl-N-(5-isopropyl-1,3-thiazol-2-yl)-1-methyl-1H-indole-5-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-6-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-5-methoxy-1H-indole-2-carboxamide;1-allyl-2-butyl-N-(5-isopropyl-1,3-thiazol-2-yl)-1H-indole-5-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-1-methyl-1H-indole-2-carboxamide;1-benzyl-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-1H-indole-5-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-1H-1,2,3-benzotriazole-5-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3,5-dimethyl-4-isoxazo 1-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-thiophenecarboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-methyl-2-thiophenecarboxarmde;N-(5-isopropyl-1,3-thiazol-2-yl)-5-methyl-2-thiophenecarboxamide;5-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)-2-thiophenecarboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-[(2,3,3-trichloroacryloyl)amino]-2-thiophenecarboxamide;5-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide;N-(5-isopropyl-1,3-thiazol-2-yl)-5-(4-nitrophenyl)-2-furamide;N-(5-isopropyl-1,3-thiazol-2-yl)-5-(2-nitrophenyl)-2-furamide;5-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide;N-(5-isopropyl-1,3-thiazol-2-yl)-5-[3-(trifluoromethyl)phenyly2ffiramide;5-(4-chloro-2-nitrophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide;N-(5-isopropyl-1,3-thiazol-2-yl)-5-(4-methyl-2-nitrophenyl)-2-furamide;5-[2-chloro-5-(trifluoromethyl)phenyl-N-(5-isopropyl-1,3-thiazol-2-yl)-2-furamide;tert-butyl(1R)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-phenylethylcarbamate;(1R)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-phenylethylacetate;(1S)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-phenylethylacetate;(R,S)-2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide;(R)-2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide;(S)-2-fluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide;2-(acetylamino)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide;(R,S)-2-(methoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide;(R)-2-(methoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide;(S)-2-(methoxy)-N-(5-isopropyl-1,3-thiazo]-2-yl)-2-phenylacetamide;3,3,3-trifluoro-N-(5-isopropyl-1,3-thiazol-2-yl)-2-methoxy-2-phenylpropanamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(1-naphthyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-naphthyl)acetamide;2-(1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;2-(1,3-benzodioxol-4-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;2-(2,4-dinitrophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-methyl-1H-indol-3-yl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(1-methyl-1H-indol-3-yl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(5-methoxy-1H-indol-3-yl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(5-benzyloxy-1H-indol-3-yl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-methoxy-2-methyl-1H-indol-3-yl)acetamide;2-(1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)-0.2-oxoacetamide;2-(5-bromo-1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;2-(5-fluoro-1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;3-(1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;4-(1H-indol-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)butanamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-(2-thienyl)propanamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-thienyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-oxo-2-(2-thienyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-thienyl)acetamide;2-(5-chloro-1-benzothiophen-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;2-(1-benzothiophen-3-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;2-[2-(formylamino)-1,3-thiazol-4-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)-2-(methoxyimino)acetamide;2-{2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl}-N-(5-isopropyl-1,3-thiazol-2-yl)-2-(methoxyimino)acetamide;2-chloro-N-(4-(2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-287.ethyl-2-({[2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-(1H-pyrazol-3-yl)ethylidene]amino}oxy)acetate;2-(2-furyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-oxoacetamide;2-(5-bromo-3-pyridinyl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(7-methoxy-2-oxo-2H-chromen-4-yl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-phenyl-3-butenamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-oxo-4-(4-methyl-phenyl)butanamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-(4-nitrophenyl)butanamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-phenylbutanamide; benzyl4-[(5-isopropyl-1,3-thiazol-2-yl)amino]-4-oxobutylcarbamatemethyl5-[(5-isopropyl-1,3-thiazol-2-yl)amino]-5-oxopentanoate;4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)butanamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-(4-methoxy-1-naphthyl)-4-oxobutanamide;3-(2-chlorophenoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;3-(4-methylphenoxy)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;3-cyclopentyl-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;3-cyclohexyl-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-methylpentanamide;3-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;3-(4-methoxyphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;3-chloro-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;3-phenyl-N-(5-isopropyl-1,3-thiazol-2-yl)propanamide;2-cyclohexyl-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-methylbutanamide;N-(5-isopropyl-1,3-thiazol-2-yl)-5-oxo-5-phenylpentanamide;2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoyl-phenylethyl acetate;N-(5-isopropyl-1,3-thiazol-2-yl)-2-[4-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)phenyl]propanamide;1-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)cyclopentanecarboxamide;1-phenyl-N-(5-isopropyl-1,3-thiazol-2-yl)cyclopentanecarboxamide;2-(3-bromo-4-methoxyphenyl)-N-(5-isopropyl 1,3-thiazol-2-yl)acetamide;2-(2-nitro-4-trifluoromethylphenyl)-N-(5-isopropyl.1,3-thiazol-2-yl)acetamide; 5-cyclohexyl1-(4-{2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethyl}benzyl)-(2S)-2-[(tert-butoxycarbonyl)amino]pentanedioate;2-(5,6-dimethyl-1H-benzimidazol-1-yl)-.N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;2-[5-(4-chlorophenyl)-2H-1,2,3,4-tetraazol-2-yl]-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-[5-(1-pyrrolidinyl)-2H-1,2,3,4-tetraazol-2-yl]acetamide;N-(5-isopropyl-1,3-thiiazol-2-yl)-2-(3-methyl-1-benzothiophen-2-yl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4,4-bis(4-methylphenyl)-3-butenamide;2-cyclopropyl-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;N-{4-bromo-6-[(5-isopropyl-1,3-thiazol-2-yl)amino]-6-oxohexyl}benzamide;2-cyclopentyl-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide; benzyl6-[(5-isopropyl-1,3-thiazol-2-yl)amino)-6-oxohexylcarbamate;N-1-(5-isopropyl-1,3-thiazol-2-yl)-N-4-(2-propynyl)-2-butenediamide;4-(2,4-dimethylphenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-4-oxobutanamide;4-(4-benzyloxyphenyl)-N-(5-isopropyl-1,3.-thiazol-2-yl)-4-oxobutanamide;4-(thiphen-2-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)-4-oxobutanamide;benzyl2-{[(benzyloxy)carbonyl]amino}-5-[(5-isopropyl-1,3-thiazol-2-yl)amino]-5-oxopentanoate;4-(1H-indol-3-yl)-N-{3-[(5-isopropyl-1,3-thiazol-2-yl)amino]-3-oxopropyl}butanamide;4-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}phenyl4-chlorobenzenesulfonate;N-(5-isopropyl-1,3-thiazol-2-yl)-4-{[(2-methoxyanilino)carbonyl)amino}benzamide;4-{[2-(isopropylsulfonyl)acetyl]amino}-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-4-{[2-(phenylsulfanyl)acetyl]amino}benzamide;4-[(diethylamino)sulfonyl]-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;2-bromo-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;3,5-difluoro-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;3-{[(2-fluoroanilino)carbonyl]amino}-N-(5-isopropyl-1,3-thiazol-2-yl)benzamide;N-(5-isopropyl-1,3-thiazol-2-yl)-1-phenyl-5-propyl-1H-pyrazole-4-carboxamide;3-chloro-4-(isopropylsulfonyl)-N-(s-isopropyl-t,3-thiazol-2-yl)-5-(methylsulfanyl)-2-thiophenecarboxamide;3-iodo-4-(isopropylsulfonyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-5-(methylsulfanyl)-2-thiophenecarboxamide;2-{[(4-chlorophenyl)sulfonyl]methyl}-N-(5-isopropyl-1,3-thiazol-2-yl)-4-methyl-1,3-thiazole-5-carboxamide;5-(4-chlorophenyl)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-(trifluoromethyl)-3-furamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,3,4,5,6-pentafluorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-fluorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-bromophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-chlorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-nitrophenyl) acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-trifluoromethylphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-methoxyphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,5-dimethoxyphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,5-difluorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4,5-trimethoxyphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,6-dichlorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-chloro-6-fluorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,5-dimethoxyphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,5-difluorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,5-bistrifluoromethylphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methylthiophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methoxyphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-bromophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-chlorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-fluorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-nitrophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-trifluoromethylphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-methylphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-dimethylaminophenyl)acetamide;2-[1,1′-biphenyl)-4-yl-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-trifluoromethylphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-bromophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-chlorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-nitrophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3-methoxyphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,4-dinitrophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,4-dichlorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2,4-difluorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-benzyloxy-3-methoxyphenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4-dichlorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4-difluorophenyl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(3,4-dimethoxyphenyl)acetamide;2-(2,3-dihydro-1H-inden-5-yl)-N-(5-isopropyl-1,3-thiazol-2-yl)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-1-phenylcyclopropanecarboxamide;2-cyclopentyl-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide;2-cyclohexyl-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenylacetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2,2-diphenylacetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(2-nitrophenoxy)acetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-nitrophenyl)propanamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl)propanamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-(4-isobutylphenyl)propanamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-oxo-2-phenylacetamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-methyl-2-phenylpentanamide;(E,Z)-N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl-2-butenamide;N-(5-isopropyl-1,3-thiazol-2-yl)bicyclo[4.2.0]octa-1,3,5-triene-7-carboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-3-oxo-1-indanecarboxamide;N-(5-isopropyl-1,3-thiazol-2-yl)-2-phenyl)butanamide; tert-butyl(1S)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-1-methyl-2-oxoethylcarbamate;tert-butyl(1S,2S)-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-2-methylbutylcarbamate;tert-butyl 2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate;tert-butyl(1S)-5-amino-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}pentylcarbamate;tert-butyl 4-[(imino{[(4-methylphenyl)sulfonyl]amino}methyl)amino]-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}butylcarbamate;tert-butyl1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl}-3-(tritylamino)propylcarbamate;tert-butyl(1S)-1-(benzyloxymethyl)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate;tert-butyl(1S)-1-benzyl-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate;tert-butyl(1R)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxo-1-(benzylthiomethyl)ethylcarbamate;benzyl(3S)-3-[(tert-butoxycarbonyl)amino]-4-[(5-isopropyl-1,3-thiazol-2-yl)amino]-4-oxobutanoate;tert-butyl(2S)-2-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl)-1-pyrrolidinecarboxylate;tert-butyl(1S)-1-(1H-indol-3-ylmethyl)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate;tert-butyl(1S)-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl)-3-(methylsulfanyl)propylcarbamate;tert-butyl(1S)-2-benzyloxy-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino]carbonyl)propylcarbamate;tert-butyl(1S)-1-(4-benzyloxybenzyl)-2-[(5-isopropyl-1,3-thiazol-2-yl)amino]-2-oxoethylcarbamate;tert-butyl(1S)-1-{[(5-isopropyl-1,3-thiazol-2-yl)amino7Jcarbonyl)-2-methylpropytcarbamate;tert-butyl(1S)-1-{[(5-isopropyl-1,3-thiazol-2-.yl)amino]carbonyl)-3-methylbutylcarbamateand; benzyl(4S)-4-[(tert-butoxycarbonyl)amino]-5-[(5-isopropyl-1,3-thiazol-2-yl)amino]-5-oxopentanoate;and the pharmaceutically acceptable salts thereof.
 7. A compound offormula (I) according to claim 1, wherein R₁ is optionally substitutedin any of the free positions by one or more groups selected from thegroup consisting of halogen, nitro, oxo groups (═O), carboxy, cyano,alkyl, perfluorinated alkyl, alkenyl, alkynyl, cycloalkyl, aryl,heterocycyl, amino groups and derivatives thereof, carbonylamino groupsand derivatives thereof, oxygen-substituted oximes, hydroxy group andderivatives thereof, carbonyl groups and derivatives thereof andsulfonated derivatives.
 8. A compound of formula (I) according to claim7, wherein said derivatives of amino groups are alkylamino,alkoxycarbonylalkylamino, dialkylamino, arylamino, diarylamino oraryleurido.
 9. A compound of formula (I) according to claim 7, whereinsaid derivatives of carbonylamino groups are hydrogencarbonylamino(HCONH—), alkylcarbonylamino, alkenylcarbonyl amino,alkenylcarbonylamino, arylcarbonylamino or alkoxycarbonylamino.
 10. Acompound of formula (I) according to claim 7, wherein saidoxygensubstituted oximes are alkoxycarbonylalkoxyimino or alkoxyimino.11. A compound of formula (I) according to claim 7, wherein saidderivatives of hydrocy groups are alkoxy, alkylcarbonyloxy,arylcarbonyloxy or cycloalkenyloxy.
 12. A compound of formula (I)according to claim 7, wherein said derivatives of carbonly groups arealkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonylcycloalkyloxycarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl.
 13. Acompound of formula (I) according to claim 1, wherein said sulfonatedderivatives are alkylthio, arylthio, alkylsulphonyl, arylsulphonyl,alkylsulphinyl, arylsulphinyl, arylsulphonyloxy, aminosulfonyl,alkylaminosulphonyl or dialkylaminosulphonyl.